Search

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

Objective: Disruptive mood dysregulation disorder (DMDD) was introduced in DSM-5 to distinguish a subset of chronically irritable youth who may be incorrectly diagnosed and/or treated for pediatric bipolar disorder (BPD). This study characterized the rate of new treatment episodes and treated prevalence of BPD and DMDD from a longitudinal electronic health record database and examined the impact of DMDD on prescription trends.Method: A retrospective cohort study using 2008-2018 Optum electronic health record data was conducted. Youth aged 10 to < 18 years with ≥ 183 days of database enrollment before the study cohort entry were included. Annual new treatment episode rates per 1,000 patient-years and treated prevalence (%) were estimated. Prescriptions for medications, concomitant diagnoses, and acute mental health service use for 2016-2018 were evaluated.Results: There were 7,677 youths with DMDD and 6,480 youths with BPD identified. Mean age (13-15 years) and ethnicity were similar for both groups. A rise in new treatment episode rates (0.87-1.75 per 1,000 patient-years, p < .0001) and treated prevalence (0.08%-0.35%, p < .0001) of DMDD diagnoses (2016-2018) following diagnosis inception was paralleled by decreasing new treatment episode rates (1.22-1.14 per 1,000 patient-years, p < .01) and treated prevalence (0.42%-0.36%, p < .0001) of BPD diagnoses (2015-2018). More youth in the DMDD group were prescribed medications compared with the BPD group (81.9% vs 69.4%), including antipsychotics (58.9% vs 51.0%). Higher proportions of youth with DMDD vs youth with BPD had disruptive behavior disorders (eg, 35.9% vs 20.5% had oppositional defiant disorder), and required inpatient hospitalization related to their mental health disorder (45.0% vs 33.0%).Conclusion: Diagnosis of DMDD has had rapid uptake in clinical practice but is associated with increased antipsychotic and polypharmacy prescriptions and higher rates of comorbidity and inpatient hospitalization in youth with a DMDD diagnosis compared with a BPD diagnosis. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate the pharmacokinetic (PK) profile and tolerability of lurasidone in children and adolescents with a range of psychiatric disorders. Methods This multicenter, open-label, single and multiple ascending-dose study of the PK profile of lurasidone (20, 40, 80, 120, and 160 mg/d) enrolled outpatients aged 6 to 17 years with a diagnosis of attention deficit/hyperactivity disorder, bipolar spectrum disorder, or other psychiatric disorder. Serial blood samples were collected for analysis of PK parameters, including C max , T max , and AUC 0–24 . Findings Exposure (C max and AUC 0–24 ) to lurasidone and its active metabolites showed linear increases across the entire dose range. Slope estimates (95% CI) across the dose range studied was 0.90 ng · h/mL (0.74–1.06) for AUC 0–24 and 0.70 ng/mL (0.52–0.87) for C max on day 10 or 12. Lurasidone exposure, after multiple-dose administration in this child and adolescent population, was similar to exposure observed at steady state in adults. The effects of dose on exposure to the 3 active metabolites of lurasidone were linear and similar after the administration of single and multiple doses. Adverse events were qualitatively similar to those reported in adults. Discontinuations due to adverse events were dose related, with doses <120 mg/d being better tolerated than higher doses, especially in younger children. Implications In this child and adolescent population, exposure parameters for lurasidone and its active metabolites were dose proportional in the range of 20 to 160 mg/d after the administration of single and multiple doses. These results suggest that lurasidone doses <120 mg/d were better tolerated compared with higher doses, especially in younger children. ClinicalTrials.gov identifier: NCT01620060. [ABSTRACT FROM AUTHOR]

Objective: To evaluate asenapine versus placebo in 403 patients aged 10 to 17 years with bipolar I disorder currently in manic or mixed episodes.Method: In this double-blind, placebo-controlled, international trial, patients were randomized 1:1:1:1 to placebo, asenapine 2.5, 5, or 10 mg b.i.d. (twice daily). Primary efficacy measure was change from baseline in Young-Mania Rating Scale (YMRS) total score at day 21. Analyses of patients with/without attention-deficit/hyperactivity disorder (ADHD) and with/without stimulant use were performed.Results: The mean difference in asenapine versus placebo in YMRS was -3.2 (p = .0008), -5.3 (p < .001), and -6.2 (p < .001) for asenapine 2.5, 5, and 10 mg b.i.d., respectively. Treatment-emergent adverse events with an incidence ≥5% and at least twice placebo were somnolence, sedation, hypoesthesia oral, paresthesia oral, and increased appetite. The asenapine groups had a higher incidence of ≥7% weight gain (range, 8.0%-12.0%) versus placebo (1.1%; p < .05). The mean change from baseline in fasting insulin was larger for patients treated with asenapine than those with placebo (asenapine 2.5 mg b.i.d.: 73.375 pmol/L; asenapine 5 mg b.i.d.: 114.042 pmol/L; asenapine 10 mg b.i.d.: 59.846 pmol/L; placebo: 3.690 pmol/L). The mean changes from baseline for lipid parameters and glucose were also larger in asenapine groups than in the placebo group. No safety differences were observed with respect to ADHD and stimulant use.Conclusion: All asenapine doses versus placebo were superior based on change in YMRS at day 21. Asenapine was generally well tolerated in patients aged 10 to 17 years with bipolar I disorder in manic or mixed states. Increases in weight and fasting insulin were associated with asenapine. Clinical trial registration information-Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder; http://clinicaltrials.gov; NCT01244815. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD).Method: After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale-Revised [CDRS-R]; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo.Results: Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was -18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was -21.95 and the mean difference vs placebo was -3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness.Conclusion: Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults.Clinical Trial Registration Information: Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the validity and reliability of a Korean version of the Parent General Behavior Inventory-10- item Mania Scale (P-GBI-10M) and the Adolescent General Behavior Inventory (A-GBI) for bipolar and depressive disorder in youths. Methods: Ninety-two subjects with mood disorder and their parents were recruited from September 2011 to June 2013 through the Department of Psychiatry at the Asan Medical Center, Seoul, Korea. In addition, 125 community participants were recruited through two middle schools and one high school in Seoul. The parents of subjects completed the Parent-version Mood Disorder Questionnaire (P-MDQ), P-GBI-10M and Attention-deficit/hyperactivity disorder Rating Scale (ARS). Adolescents complete the 76-item A-GBI, Beck Depression Inventory (BDI), and Adolescent version of the Mood Disorder Questionnaire (A-MDQ). Results: Different profiles were evident between the clinic-referred group and the community control, including different P-GBI-10M (t = 3.07, p = 0.003), A-GBI Depressive (t = 4.99, p b 0.001), Hypomanic/Biphasic subscales (t = 3.17, p = 0.002), and BDI (t = 4.76, p b 0.001) scores. The A-GBI Depressive subscale score (t = 3.02, p = 0.003), BDI score (t = 2.12, p = 0.037) and A-GBI Hypomanic/ Biphasic subscale score (t = 2.71, p = 0.008) were significantly different between patients with bipolar disorder and those with depressive disorder. Of the 73 items of the Depressive and Hypomanic/Biphasic subscales of the A-GBI, eight discriminated between bipolar and depressive disorder. Furthermore, A-GBI Depressive subscale scores were significantly correlated with BDI (r = 0.81, p b 0.001), A-GBI Hypomanic/Biphasic subscale (r = 0.88, p b 0.001), A-MDQ (r = 0.58, p b 0.001), P-MDQ (r = 0.22, p = 0.005), and ARS (r = 0.26, p b 0.001) scores. Cronbach's α of the A-GBI was 0.98. Conclusion: The Korean version of the Parent and Adolescent General Behavior Inventories showed excellent internal consistency, fair-togood construct, and discriminant validity. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To examine health-related quality of life (HRQoL) in adolescents with bipolar disorder before and after double-blind treatment with olanzapine or placebo. Methods: Parents or legal guardians of 160 adolescents with a manic or mixed episode associated with bipolar I disorder were asked to rate their child''s health using the Child Health Questionnaire-Parental Form 50 at baseline, before receiving medication, and then again at the end of participation in a 3-week double-blind placebo-controlled study of olanzapine. Results: Adolescents in both treatment groups began and ended the study with significantly lower scores than normalized values of healthy peers on several HRQoL subscales (lower ratings indicate more impaired functioning), especially those assessing psychosocial factors. However, participants receiving olanzapine exhibited greater improvement than those in the placebo group across multiple HRQoL subscales, including the Behavior, Family activities, and Mental health subscales. Reduction in manic symptoms was associated with improvement in HRQoL values. Conclusions: As expected, manic adolescents with bipolar disorder exhibit abnormalities in psychosocial, rather than physical factors associated with HRQoL. Treatment with olanzapine had a greater effect on multiple domains of psychosocial functioning compared with placebo, suggesting that in addition to improving manic symptoms, pharmacologic interventions may lessen some of psychosocial deficits experienced by adolescents with bipolar disorder. However, following 3 weeks of treatment, adolescents with bipolar disorder continued to exhibit deficits in several aspects of psychosocial functioning, indicating that additional pharmacologic and psychosocial interventions may be necessary to further improve functional outcome. [Copyright &y& Elsevier]

The article presents a research study concerning the effectiveness and safety of lisdexamfetamine dimesylate (LDX) versus placebo for the treatment of attention-deficit hyperactivity disorder (ADHD) among adolescents. It notes that the findings of the study reveal that adolescents who are under LDX therapy exhibit improvements. The findings also suggest that LDX is more effective and safer than placebo in treating ADHD among adolescents.

The article presents a study which examines the effectiveness and safety of three antipsychotics in the treatment of early-onset schizophrenia spectrum (TEOSS). A total of 116 youths age 8 to 19 years underwent an 8-week, randomized, acute trial of molindone, olanzapine and risperidone and standardized symptom and functional assessments were carried out every four weeks. The result show that the three treatment agents have no significant differences in time discontinuation or symptom decrease.

Abstract: Background: Short-term treatment with the meth-ylphenidate transdermal system (MTS) has been well tolerated in several clinical trials in children with attention-deficit/hyperactivity disorder (ADHD). However, the effects of long-term use have not been systematically evaluated. Objectives: The primary objective of this study was to assess the 12-month tolerability of MTS in children with ADHD. Effectiveness was a secondary objective. Methods: This Phase III study was a multicenter, 12-month, open-label, flexible-dose extension of 4 previous trials. In those studies, children aged 6 to 12 years with a diagnosis of ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria) received MTS, osmotic-release oral system methylphenidate, or placebo. At entry into the present study, the children either continued to receive their optimal dose of MTS (10, 15, 20, or 30 mg per 9-hour patch wear time) or underwent dose titration over 4 weeks to an optimal MTS dose, which was continued for the remainder of the study. Tolerability was evaluated based on adverse events (AEs), physical examinations, vital signs, electrocardiograms, laboratory tests, the Children''s Sleep Habits Questionnaire, and the occurrence of application-site reactions. Results: Of 327 enrolled subjects, 326 received treatment and 157 completed the study. The majority of enrolled subjects were male (64.8%) and white (73.7%), with a mean (SD) age of 9.2 (1.9) years. Two hundred sixty-five (81.3%) of the 326 subjects who received MTS reported AEs. AEs led to study discontinuation in 29 subjects (8.9%). The majority (98.3%) of treatment-emergent AEs were of mild or moderate severity. The most common AEs were decreased appetite (24.8%), headache (16.6%), upper respiratory tract infection (12.3%), cough (11.7%), pyrexia (10.1%), and decreased weight (10.1%). Of the 1118 AEs, 40.8% were considered possibly or probably related to study treatment. Three serious AEs (facial contusion, ankle fracture, and syncope) occurred and were considered unrelated to study treatment. Based on data collected across all study visits, application-site reactions generally consisted of mild erythema associated with mild discomfort at the patch site. Application-site reactions accounted for 22 (6.7%) study discontinuations. Conclusions: Slightly less than half (48.0%) of subjects completed this 12-month, open-label extension study of MTS. Most AEs were mild to moderate in severity and, with the exception of application-site reactions, were typical of those previously observed with methylphenidate. [Copyright &y& Elsevier]

Abstract: Background: Efficacious and well-tolerated medications are available for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulants such as methylphenidate (MPH) and amphetamines are the most widely used medications approved by the US Food and Drug Administration for the treatment of ADHDin children. Objective: This article reviews the literature on the development and use of medications for the treatment of ADHD in children. Methods: A search of MEDLINE was conducted toidentify relevant studies and critical reviews on the treatment of ADHD in children.The main criteria for inclusion of a study were that it have a controlled design, enroll >100 subjects if a clinical trial and >20 subjects if a classroom study, assess symptoms with the most widely used scales and tests,and be published from 2000 to 2008.A few older pivotal studies were also included. Results: Many studies have reported the long-term efficacy and tolerability of immediate-release formulations of MPH. The disadvantages of such formulations include the need for multiple daily dosing and a potential for abuse. Various extended-release formulations of MPH have been found effective in controlled studies enrolling large numbers of children with ADHD. The efficacy and tolerability of dexmethylphenidate, the active D-isomer of MPH, in an extended-release formulation have also been reported. An extended-release formulation of mixed amphetamine salts (MMAS-XR) that is dosed once daily has been found to be efficacious and well tolerated. The non-stimulant atomoxetine has been reported to be well tolerated and efficacious, although it may not be as effective as stimulants; this formulation is, however, less likely than stimulants to be associated with abuse and diversion. A recently approved prodrug stimulant, lisdexamfetamine dimesylate (LDX), was developed to provide a long duration of effect that is consistent throughout the day, with a reduced potential for abuse. In a placebo-controlled study in children with ADHD, less intersubject variability in Tmax, Cmax, and AUC from time zero to the last quantifiable concentration was seen in the 8 subjects who received LDX (percent coefficient of variation, 15.3, 20.3, and 21.6, respectively) compared with the 9 subjects who received MAS-XR (52.8, 44.0, and 42.8).In 2 clinical trials, significantly greater improvements in teacher and parent ratings of ADHD symptoms were seen with LDX compared with placebo (P<0.001).A study of the abuse potential of LDX evaluated subjective responses to the effects of oral LDX and immediate-release d-amphetamine in adults with a history of stimulant abuse. LDX was associated with a significantly lower abuse-related liking effect than d-aamphetamine (P = 0.039). Conclusions: Currently available treatments for ADHD in children are efficacious and well tolerated, but many of them are limited by the requirement for multiple daily dosing and abuse potential. LDX, a long-acting prodrug of d-amphetamine, has been reported to be effective and appears to overcome some of these limitations. [Copyright &y& Elsevier]

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. Patients received 1 week each of placebo, methylphenidate 5 mg twice daily, methylphenidate 10 mg twice daily, and methylphenidate 15 mg twice daily using a crossover design. Subjects were randomly assigned to receive one of six possible dosing orders. At study's end, and before the blind being broken, a "best dose week" for each subject was determined. The primary outcome measure was the total score on the parent-completed ADHD Rating Scale-IV.Results: Sixteen patients, with a mean age of 10.43 (SD 3.14) years completed the trial. Lower scores during best dose treatment compared to the week of placebo treatment were found on the ADHD Rating Scale-IV (p < .05), suggesting a therapeutic benefit. A large effect size (Cohen's d = 0.90) was found for methylphenidate. Treatment was generally well tolerated.Conclusions: Euthymic youths with bipolar disorder and ADHD may benefit from short-term concomitant treatment with methylphenidate. [ABSTRACT FROM AUTHOR]

The article focuses on the case study of a 9-year-old boy having reactive and impulsive aggressive behavior for the last 2 years. He was treated with OROS methylphenidate by his pediatrician and moderate improvement was noted in his symptoms of attention-deficit/hyperactivity disorder (ADHD). But in his aggression, only minimal improvement occurred.

Objective: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001.Method: Participants received venlafaxine ER (flexible dose, based on body weight; intent to treat, n = 169) or placebo (intent to treat, n = 165) for up to 8 weeks. The primary efficacy variable was the change from baseline in the Children's Depression Rating Scale-Revised score at week 8.Results: There were no statistically significant differences between venlafaxine ER and placebo on the Children's Depression Rating Scale-Revised in either study. A post hoc age subgroup analysis of the pooled data showed greater improvement on the Children's Depression Rating Scale-Revised with venlafaxine ER than with placebo (-24.4 versus -19.9; p = .022) among adolescents (ages 12-17), but not among children (ages 7-11). The most common adverse events were anorexia and abdominal pain. Hostility and suicide-related events were more common in venlafaxine ER-treated participants than in placebo-treated participants. There were no completed suicides.Conclusions: Venlafaxine ER may be effective in depressed adolescents. However, its safety and efficacy in pediatric patients has not been established. Prescribers should monitor for signs of suicidal ideation and hostility in pediatric patients taking venlafaxine ER. [ABSTRACT FROM AUTHOR]

The article analyzes the use of clozapine in the treatment of children and adolescents. Clozapine has been described in several pediatric patient populations. The article holds that clozapine therapy is an alternative for some pediatric patients with psychotic disorders or bipolar illnesses who do not respond to other forms of pharmacotherapy.

The article presents a study in the U.S., which is aimed to provide an initial description of the effectiveness and pharmacokinetics of quetiapine in aggressive children with conduct disorder. The researchers conducted an eight-week clinical trial among patients ages 6-12 years. Preliminary data suggests that aggressive children with conduct disorder may benefit from quetiapine.

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. Patients ages 5 to 17 years with bipolar disorder type I or II, who had achieved symptom remission with Li/DVPX combination therapy and subsequently relapsed during treatment with Li or DVPX monotherapy were enrolled between January 1999 and January 2003.Results: Thirty-eight patients with a mean age of 10.5 years entered the study. Thirty-four (89.5%) patients responded to treatment with Li/DVPX mood stabilizer therapy alone, but four patients required adjunctive antipsychotic treatment to address residual symptomatology. Overall, reinitiation of Li/DVPX combination therapy was well tolerated with no subjects discontinuing because of a medication-related adverse event.Conclusions: It appears that most youths with bipolar disorder who stabilize on combination Li/DVPX therapy and subsequently relapse during monotherapy can safely and effectively be re-stabilized with the reinitiation of Li/DVPX combination treatment. [ABSTRACT FROM AUTHOR]

Objective: To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR®) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). Study design: Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced–dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n=580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. Results: Changes in blood pressure, pulse, and QT interval corrected by Bazett''s formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. Conclusions: Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of ≤ 30 mg/day in otherwise healthy children. [Copyright &y& Elsevier]

This article presents information on a case study related to pharmacological management of agitation and aggression in an adolescent with autism. A 13-year-old boy with autism and severe mental retardation presented to the inpatient psychiatric unit due to a recent increase in agitation and physical aggression. Following the closure of his group home, he moved to a similar one. He has not adjusted well to the changes in setting and staff. A behavioral specialist began working with the patient and the group home staff to address his increased pacing, anger outbursts, and minor physical aggression. When he struck a staff member, he was transported to the emergency department and psychiatrically hospitalized. Current medications include paroxetine 20 mg each morning, divalproex sodium 250 mg twice daily, and quetiapine 50 mg twice daily.

Objective: To assess the efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type I. Method: This double-blind, placebo-controlled study was discontinued early when adult mania trials with topiramate failed to show efficacy. Efficacy end points included the Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale for Children, Children's Depression Rating Scale, Children's Global Assessment Scale, and Clinical Global Impressions-Improvement. Results: Fifty-six children and adolescents (6-17 years) with a diagnosis of bipolar disorder type I received topiramate (n = 29, 52%) or placebo (n = 27, 48%). The only statistically significant differences in efficacy measures between treatment groups were the difference between slopes of the linear mean profiles of the YMRS (p= .003) using a post hoc repeated measures regression and the change in Brief Psychiatric Rating Scale for Children at day 28 (-14.9 versus -5.9, p = .048) using observed data. Adverse events with topiramate included decreased appetite, nausea, diarrhea, and paresthesia. Conclusions: Topiramate was well tolerated; however, the results are inconclusive because of premature termination resulting in a limited sample size. Adequately powered controlled trials are necessary to determine whether topiramate has efficacy in reducing symptoms of acute mania in children and adolescents. [ABSTRACT FROM AUTHOR]

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 11 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. Study participation ended if the subject required additional clinical intervention or if the subject did not adhere to study procedures. Results: Patients were recruited between July 1998 and May 2002. One hundred thirty-nine youths with a mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean (SD) duration of 10.7(5.4) weeks. Sixty youths were then randomized to receive monotherapy with Li+(n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups did not differ in survival time until emerging symptoms of relapse (p = .55) or survival time until discontinuation for any reason (p = .72). conclusions: DVPX was not found to be superior to Li+ as maintenance treatment in youths who stabilized on combination Li+/DVPX pharmacotherapy. [ABSTRACT FROM AUTHOR]

Recent evidence from the Treatment for Adolescents With Depression Study (TADS) suggests that combining cognitive behavioral and pharmacological treatments holds the most promise for ameliorating depression among adolescents. This article describes lessons learned during the TADS trial about how to integrate these two treatments in the care of adolescents with depression. Toward this end, both common and unique components of each perspective''s approach to data gathering and treatment selection are presented. Procedures for changing “dosage” and adding adjunctive treatments to each of these interventions are also discussed. Finally, issues related to sequencing treatments and guidelines for sharing information across treatment providers are offered. [Copyright &y& Elsevier]

Objective: To compare the diagnostic efficiency of six index tests as predictors of juvenile bipolar disorder in two large outpatient samples, aged 5 to 10 and 11 to 17 years, gathered from 1997 to 2002.Method: DSM-IV diagnosis was based on a semistructured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children) with the parent and youth sequentially, blind to scores on the index tests. Participants were 318 youths aged 5 to 10 (50% with bipolar diagnoses) and 324 youths aged 11 to 17 (41% with bipolar diagnoses). Areas under the curve (AUCs) from receiver operating characteristic analyses and multilevel likelihood ratios quantified test performance.Results: Parent report (AUCs from 0.78 to 0.84 in both age groups) outperformed teacher (AUCs 0.57 in the younger sample and 0.70 in the older sample) or adolescent measures (AUCs 0.67 [General Behavior Inventory] and 0.71 [Youth Self-Report]) at identifying bipolar disorders. Combining tests did not produce clinically meaningful classification improvement.Conclusions: Parent report was more useful than teacher report or adolescent self-report on the index tests studied. Results generally replicated across both age groups. Parent report on these instruments could facilitate differential diagnosis of bipolar disorder in youths aged 5 to 17 years, especially by decreasing the rate of false-positive diagnoses. [ABSTRACT FROM AUTHOR]

Despite the severity of bipolar disorder (BP) and the amount of attention the psychosocial treatment of BP among adults has been given (e.g., ; ), no published outcome study or psychosocial treatment manual to date exists for children with this disorder. Based upon what is known about the phenomenology of BP in adolescents and what has been published with regard to existing treatments and their efficacy for adults with BP and adolescents with unipolar depression, the purpose of this article is to describe a model for an empirically driven cognitive behavioral treatment for BP in adolescents. The manualized intervention described herein includes the following intervention components: psychoeducation, medication compliance, mood monitoring, anticipating stressors and problem solving, identifying and modifying unhelpful thinking, sleep regulation and relaxation, and family communication. In addition, optional modules devoted to substance abuse, social skills, anger management, and contingency management are offered. The treatment includes a 12-session acute phase of treatment, followed by a maintenance phase and biyearly “booster” sessions. The rationale for and format of each session is presented. Currently, a pilot study is under way to evaluate the preliminary efficacy of this treatment for adolescents with BP. To illustrate the treatment, we present a case study including outcome data for a 13-year-old boy with bipolar I. [Copyright &y& Elsevier]

Both simple attention tasks (e.g. letter cancellation) and most tasks of higher cognitive processing (e.g. word generation) are known to activate the dorsolateral prefrontal cortex (PFC). While attention and higher cognitive processing differ phenomenologically, with attention tasks requiring great subjective effort despite their simplicity, possible physiological differences in the activation of the PFC between the two types of cognitive processing have remained uninvestigated. Hemodynamic changes in the PFC during activation due to tasks of attention and those of higher cognitive processing were examined using near-infrared spectroscopy in 10 Japanese and 10 American healthy adults. In tasks of higher cognitive processing, which included both verbal and non-verbal tasks, the concentration of oxygenated hemoglobin ([HbO2]) increased, and that of deoxygenated hemoglobin ([HbR]) decreased, with an increase in the tissue hemoglobin saturation (THS). In tasks of attention, which consisted of the letter cancellation and continuous performance test, both [HbO2] and [HbR] increased, with no significant changes in the THS observed. The distinctive patterns of hemodynamic changes were not affected by the factors of task difficulty or language. The change in [HbR] may be a physiological marker of the prefrontal lobe activation that discriminates between attention and higher cognitive processing. The increase in [HbR] suggests increased oxygen consumption of the PFC during tasks of attention, which might be related to the disproportionately great subjective effort associated with sustained attention. The physiological alteration in hemodynamic patterns according to changes in cognition needs to be examined in subjects with prefrontal lobe dysfunction, such as schizophrenia and mood disorder. [Copyright &y& Elsevier]