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Objective: Understanding placebo response is a prerequisite to improving clinical trial methodology. Data from placebo-controlled trials of atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) were analyzed to identify demographic and clinical characteristics that might predict placebo response in future clinical trials. Method: Data were pooled across 731 placebo-treated pediatric patients who participated in 10 acute, randomized, placebo-controlled trials. Responder status was based on empirically derived thresholds of change on the total score of the ADHD Rating Scale with minimal and robust response defined as 25% or greater and 40% or greater decrease, respectively. Study design characteristics, including randomization ratio, dose, and titration strategy, and patient demographic and clinical characteristics were examined as potential predictors of placebo response. Results: Inattentive subtype, lack of previous stimulant treatment, presence of comorbid tics and nonwhite ethnicity were associated with robust placebo response. A subset analysis of patients completing 6 weeks of treatment (to eliminate the effects of early dropout) identified inattentive subtype and lack of previous stimulant experience as significant predictors of robust placebo response. Conclusions: Placebo response is less likely in subjects with combined-subtype ADHD who are not stimulant-naive. Limiting ADHD clinical trials to this more restricted subject group is likely to maximize treatment differences. However, because this is not always possible or desirable, identifying other methods of mitigating placebo response is essential. (Contains 2 tables.)

Data from six randomized controlled trials in the U.S. reveal that 47 percent of patients aged six to 18 years showed a much improved clinical response to atomoxetine as a treatment for attention deficit hyperactivity disorder while 40 percent did not have a response. Augmenting or switching treatment in non-responders by week 4 is suggested.

Objectives. Atomoxetine seems to be as effective for treating attention-deficit/hyperactivity disorder (ADHD) when the daily dose is administered once in the morning as when the dose is divided and administered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening and early morning. Another goal was to determine how early in treatment it was possible to discern a specific effect of the drug on ADHD symptoms. Methods. This study was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 12 outpatient sites in the United States. A total of 197 children, 6 to 12 years of age, who had been diagnosed as having ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, were randomized to receive 8 weeks of treatment with atomoxetine or placebo, dosed once daily in the mornings. ADHD symptoms were assessed with parent and investigator rating scales. The primary outcome measure was the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score. Daily parent assessments of children's home behaviors in the evening and early morning were recorded with an electronic data entry system. This instrument measures 11 specific morning or evening activities, including getting up and out of bed, doing or completing homework, and sitting through dinner. Results. Seventy-one percent of the children enrolled were male, 69% met criteria for the combined subtype (both inattentive and hyperactive/impulsive symptoms), and the most common psychiatric comorbidity was oppositional defiant disorder (35%). Once-daily atomoxetine (final mean daily dose of 1.3 mg/kg) was significantly more effective than placebo in treating core symptoms of ADHD. Mean reductions in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score were significantly greater for patients randomized to atomoxetine, beginning at the first visit after the initiation of treatment and continuing at all subsequent visits. Both inattentive and hyperactive/impulsive symptom clusters were significantly reduced with atomoxetine, compared with placebo. With continued treatment and dose titrations, core symptoms of ADHD continued to decrease throughout the 8-week study. Mean reductions in the daily parent assessment total scores for patients randomized to atomoxetine were superior during the first week, beginning with the first day of dosing, and were also superior at endpoint. Efficacy outcomes for the evening hours for atomoxetine-treated patients were superior to those for placebo-treated patients, as assessed with 2 different assessment scales. Decreases in the daily parent assessment morning subscores at endpoint showed a significant reduction in symptoms that lasted into the mornings. Rates of discontinuations attributable to adverse events were Conclusions. Among children 6 to 12 of age who had been diagnosed as having ADHD, once-daily administration of atomoxetine in the morning provided safe, rapid, continuous, symptom relief that lasted not only into the evening hours but also into the morning hours. Atomoxetine treatment was safe and well tolerated. Pediatrics 2004;114:e1--e8. URL: http.//www.pediatrics.org/ cgi/content/full/114/1/el; atomoxetine, ADHD, children, continuous relief, once-daily, rapid onset of action.

The article details a study which examined the common genetic variations associated with symptomatic improvement in patients with bipolar I depression. The study included 88 olanzapine/fluoxetine combination (OFC)-treated and 85 lamotrigine-treated patients. It found that SNP within the dopamine D3 receptor and histamine H1 receptor (HRH1) genes influence response to OFC, while SNP within the dopamine D3 receptor, HRH1, dopamine-Β-hydroxylase and glucocorticoid receptor influence lamotrigine response.

Quantitative description of spatial patterns is often at the heart of ecological research in aquatic systems, particularly for investigations of how biota respond to physical habitat. A common first step for approximating a river channel is tessellation, or the discretization of the channel into cells of approximately uniform size, and assigning each cell a representative value for velocity or other characteristics. More innovative methods may use the fractal dimension to characterize patterns of features in spatially complex geological structures, such as channel bed forms. Unfortunately, these methods lose information because they either force continuous data into a grid framework or assume that complexity is constant over a range of scales. The current understanding of aquatic processes would improve if information about the scale of channel features could be preserved throughout the analysis instead of being discarded in the first step because simplifying assumptions were used. New methods are presented that characterize complex spatial data sets with minimal use of assumptions or simplifying approximations. The new methods identify dominant featuresin a set of coordinate data, locate the positions of such features in the cross section, describe how kinetic energy is distributed in these features, and quantify how features of different scales relate toone another. The effectiveness of this technique on mathematical constructs having known characteristics is demonstrated. The methods arethen used to describe a Missouri River cross section before and after river regulation to illustrate how the methods can be used to quantify changes in physical habitat patterns that may not be apparent using other methods. Improved description of complex shapes in aquatic environments may lead to increased understanding of aquatic processes in general, and in particular, the way aquatic organisms relate to physical habitat. [ABSTRACT FROM AUTHOR]