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AbstractObjective:The aim of this study was to evaluate the tolerability and effectiveness of the methylphenidate transdermal system (MTS) over 6 months in adolescents with attention-deficit/hyperactivity disorder (ADHD).Methods:This was an industry-sponsored, 30-center, open-label study of subjects aged 13–17 years with ADHD. Subjects were dose-optimized with MTS (10–30 mg/9 hours) over 5 weeks and then dose-maintained for up to 5 months. Tolerability evaluations included treatment-emergent adverse events (TEAEs) and dermal responses. Effectiveness was assessed with the ADHD-Rating Scale-IV (ADHD-RS-IV).Results:A total of 162 subjects received MTS treatment. The majority of TEAEs (>99%) were mild or moderate in intensity, and the most frequently reported TEAE was decreased appetite (15.4%). Thirteen subjects discontinued the study due to TEAEs. The majority (93.6%) of dermatologic reactions indicated mild erythema. There was significant improvement in mean ADHD-RS-IV total scores from study entry to end point (p< 0.001).Conclusion:Slightly more than half (54.0%) of subjects completed this 6-month, open-label extension study of MTS; the primary reason for discontinuation was withdrawn consent (36.0%). Reported TEAEs and skin tolerability findings were similar to those observed with MTS use in children and adolescents. MTS treatment resulted in a decrease in ADHD symptoms as rated by clinicians.NIH Clinical Trials Registry:# NCT00501293 [ABSTRACT FROM AUTHOR]

AbstractObjective:The aim of this study was to assess the effectiveness and safety of lisdexamfetamine dimesylate (LDX) in children with attention-deficit/hyperactivity disorder (ADHD).Method:This was a 7-week, open-label study evaluating 20, 30, 40, 50, 60, or 70 mg/day LDX in 318 children aged 6–12 years with ADHD. The ADHD Rating Scale IV (ADHD-RS-IV) was the primary efficacy assessment. Secondary measures included the Clinical Global Impressions–Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), and Behavior Rating Inventory of Executive Function (BRIEF). Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.Results:At end point, mean (standard deviation [SD]) improvement from baseline in ADHD-RS-IV total score was 28.6 (10.9) (p< 0.0001). Most subjects (89.9%) were rated “improved” (i.e., CGI-I 1 or 2). Improvements from baseline were observed in the EESC total and subscale scores (p≤ 0.0002). LDX treatment resulted in significant improvement on the Global Executive Composite, Behavioral Regulation, and Metacognition indices of the BRIEF (p< 0.0001). TEAEs (incidences ≥10%) were decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia.Conclusions:LDX was effective and generally well tolerated with a safety profile consistent with long-acting stimulant use. There was overall improvement in ADHD symptoms and executive function measures and no worsening of emotional expression measures.Trial Registration:clinicaltrials.gov Identifier: NCT00500071. [ABSTRACT FROM AUTHOR]

AbstractObjectives:This study evaluated flexible-dose pharmacokinetics, safety, and effectiveness of aripiprazole in children and adolescents with conduct disorder (CD).Methods:This open-label, 15-day, three-center study with an optional 36-month extension enrolled a total of 23 patients: 12 children (6–12 years) and 11 adolescents (13–17 years) with CD and a score of 2–3 on the Rating of Aggression Against People and/or Property (RAAPP). Initially, the protocol used the following dosing: subjects 50–70 kg, 10 mg/day; and subjects >70 kg, 15 mg/day. Due to vomiting and sedation, this schedule was revised to: 50–70 kg, 5 mg/day; and >70 kg, 10 mg/day.Results:Aripiprazole pharmacokinetics were linear, and steady state appeared to be attained within 14 days. Both groups demonstrated improvements in RAAPP scores and Clinical Global Impressions–Severity (CGI-S) scores. Adverse events were similar to the known profile for aripiprazole in adults.Conclusion:The pharmacokinetics of aripiprazole in children and adolescents are linear and comparable with those in adults. Aripiprazole was generally well-tolerated in patients with CD, particularly after protocol adjustments, with improvements in aggressive behavior. [ABSTRACT FROM AUTHOR]

AbstractObjective:The 2006 Research Forum addressed the goal of formulating a research agenda for early-onset bipolar disorder (EOBP) and improving outcome by understanding the risk and protective factors that contribute to its severity and chronicity.Method:Five work groups outlined barriers and research gaps in EOBP genetics, neuroimaging, prodromes, psychosocial factors, and pharmacotherapy.Results:There was agreement that the lack of consensus on the definition and diagnosis of EOBP is the primary barrier to advancing research in BP in children and adolescents. Related issues included: the difficulties in managing co-morbidity both statistically and clinically; acquiring adequate sample sizes to study the genetics, biology, and treatment; understanding the EOBP's developmental aspects; and identifying environmental mediators and moderators of risk and protection. Similarly, both psychosocial and medication treatment strategies for children with BP are hamstrung by diagnostic issues. To advance the research in EOBP, both training and funding mechanisms need to be developed with these issues in mind.Conclusions:EOBP constitutes a significant public health concern. Barriers are significant but identifiable and thus are not insurmountable. To advance the understanding of EOBP, the field must be committed to resolving diagnostic and assessment issues. Once achieved, with adequate personnel and funding resources, research into the field of EOBP will doubtless be advanced at a rapid pace. [ABSTRACT FROM AUTHOR]

AbstractChildren 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. As a result, future treatment studies in this population appear to be warranted, not only due to the putative impending risk of developing bipolar disorder, but also the manifest risk of current depressive episodes. [ABSTRACT FROM AUTHOR]

AbstractObjective: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). The Conners' Continuous Performance Test II, Reading and Math Fluency subscales of the Woodcock-Johnson III Tests of Achievement, and the Stroop Color and Word Test were administered at baseline and end of study.Results:Fourteen (9 males and 5 females) youths were diagnosed with ADHD-combined type, while 9 (5 males and 4 females) were diagnosed with ADHD-inattentive type. At a mean dose of 6.7 mg/day, end of study results showed overall significant improvement from baseline on ADHD and functional outcome measures. No significant differences in baseline performance at end of study were found on the cognitive measures. The most frequently reported adverse events were sedation (n 18; 78.3) and headache (n 11; 47.8).Conclusions:Although this was a brief pilot study with a small sample size, in this cohort, APZ led to clinical benefit in reducing ADHD symptoms and improving overall functioning. Of note, cognitive functioning did not appear to be negatively impacted by APZ treatment. [ABSTRACT FROM AUTHOR]

ObjectiveThe objectives of this pilot study were to explore the changes in symptom severity, tolerability, and the pharmacodynamics of venlafaxine treatment in youths with attention-deficithyperactivity disorder (ADHD).MethodsThis was a 2-week, open-label, outpatient trial of venlafaxine in children and adolescents, ages 5–17 years, with ADHD. Three dosing strata, 0.5, 1.0, and 2.0 mgkg per day, were examined. ADHD symptom severity and improvement assessments included the ADHD Rating Scale (ARS-IV) and the Clinical Global Impressions Scale (CGI). During this study, venlafaxine, O-desmethylvenlafaxine (ODV), norepinephrine, and serotonin concentrations were obtained.ResultsThirty-eight participants (33 males) were treated in this trial. Overall, parent-completed and teacher-completed ARS-IV total scores showed a statistically significant positive change at the end of the study when compared to baseline (p< 0.05). Significant increases in plasma venlafaxine concentrations were observed at day 15 when compared to day 8 (p 0.04). In addition, plasma norepinephrine and serotonin concentrations were found to be significantly decreased from baseline at end of study (p< 0.05). Four patients ended participation in the study prematurely lost to follow up (n 2), withdrawal of consent (n 1), and worsening of ADHD symptoms after 8 days of treatment (n 1). There were no discontinuations due to other adverse events.ConclusionsVenlafaxine appeared to offer some benefit and appears to be relatively safe for the short-term treatment of ADHD in this open-label trial. The pharmacodynamics of venlafaxine in youths are consistent with serotonergic and neuradrenergic modulation. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study was to compare clinical and health services outcomes in pediatric inpatients prescribed an atypical antipsychotic (AA) to those not prescribed an AA at discharge.MethodsDescriptive statistics, analysis of variance (ANOVA), and, where necessary, analysis of covariance (ANCOVA) were used to compare differences between and within an inpatient group prescribed risperidone, olanzapine, or quetiapine (n 1,131) with an inpatient group not prescribed an antipsychotic at discharge (n 1,741).ResultsThe AA treatment group showed greater psychiatric symptom difficulty at admission as measured by the Brief Psychiatric Rating Scale for Children (Mean BPRS-C) than the group not prescribed AAs (40.3 [n 433] vs. 35.2 [n 452], respectively, p< 0.001). AA-treated inpatients also had a higher number of mental health outpatient visits during the 6 months prior to admission. Patients receiving AAs (n 1,050) had significantly longer adjusted length of stay (LOS) than those not receiving antipsychotics (n 1,664) 26.4 days versus 22.4 days, respectively (p< 0.04).ConclusionsThe findings suggested pediatric inpatients presenting with greater psychiatric symptom difficulty at hospital admission were more likely to be prescribed an AA. Choice of AA may influence certain clinical and health services outcomes. Additional prospective controlled studies evaluating AA efficacy and safety, including head-to-head comparisons, in pediatric inpatients are warranted. [ABSTRACT FROM AUTHOR]

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, openlabel, outpatient quetiapine trial. Psychometric measures included the Rating of Aggression Against People and/or Property Scale (RAAPP), the Nisonger Child Behavior Rating Form (NCBRF), the Conners' Parent Rating Scale (CPRS-48), the Clinical Global Impressions Scale of Severity (CGI-S), and the Children's Global Assessment Scale.Results:Nine males with a mean age of 8.9 (SD = 1.2) years were treated. The median quetiapine dose at end of study was 150 mg/day (range 75–350). Mean psychometric scores did not change substantively from baseline. No patients experienced extrapyramidal side effects. Three subjects discontinued due to study nonadherence. No patients discontinued treatment due to an adverse event.Conclusions:These preliminary data suggest that quetiapine might be a generally safe and effective maintenance treatment for aggressive children with CD who initially respond to an acute therapeutic trial of quetiapine. More research is needed to confirm or refute these initial findings. [ABSTRACT FROM AUTHOR]

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. Memantine oral solution (2 mg/mL) was titrated to 10 mg/day (n= 8) or 20 mg/day (n= 8). Safety data and blood samples for pharmacokinetic analyses were collected. The ADHD Rating Scale-IV (ADHD-IV) and Clinical Global Impression of Severity (CGI-S) scale measured the effectiveness of memantine.Results:There were no discontinuations due to adverse events (AEs), serious AEs, deaths, or suicides. Most AEs were mild and occurred during the first week of treatment. The 20 mg/day memantine dose was associated with a higher rate of completion and larger mean improvement on the ADHD-IV and CGI-S than 10 mg/day memantine. Pharmacokinetic analyses suggest response to memantine may be dose-dependent beyond an initial threshold concentration.Conclusions:This pilot study suggests that a memantine dose of 20 mg/day may be a safe and possibly effective treatment for pediatric ADHD. Further investigations of memantine in ADHD appear to be warranted. [ABSTRACT FROM AUTHOR]