The evidence-based pharmacological treatment of paediatric ADHD.

Attention deficit hyperactivity disorder (ADHD) is common in children, adolescents, and adults, with extensive research establishing it as a valid neurobiological disorder. Without intervention, ADHD can result in significant impairment throughout the lifespan for the individuals it afflicts. Fortunately, multiple evidence-based options are available for the treatment of ADHD, including several efficacious pharmacotherapies. The role of medication, including stimulants as well as non-stimulants, is well-documented by an extensive body of literature. Although there may be less enthusiasm for behavioural and other psychosocial interventions as stand-alone treatments for moderate to severe ADHD, they are recommended as first-line treatment for ADHD management in preschool-aged children, for those patients with mild symptoms, and as an adjunct to medication in patients with comorbid disorders or suboptimal responses to pharmacotherapy. When planning treatment for individuals with ADHD, the potential risks associated with the available interventions must be carefully balanced against the risks of not treating, or not treating adequately. The treatment plan must also include ongoing re-assessment of the effectiveness of and the need for continued therapy. Recent practice parameters provide further specific guidance for the evidence-based assessment and treatment of children and adolescents with ADHD

Atomoxetine treatment in children and adolescents with attention-deficit hyperactivity disorder: what are the long-term health-related quality-of-life outcomes?

OBJECTIVE: Numerous investigations have examined the efficacy of pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in children. However, relatively few studies have addressed the impact of treatment on long-term subjective, psychosocial outcomes, such as health-related quality of life (HRQL). This study examines the long-term effects of pharmacological treatment with atomoxetine on HRQL in children and adolescents with ADHD. METHODS: Participants included 6- to 17-year-old children and adolescents (n = 912) with ADHD enrolled in a 24-month, multicenter, open-label trial of atomoxetine. Outcomes included clinician ratings of ADHD, parent ratings of ADHD, and a widely used measure of HRQL (The Child Health Questionnaire (CHQ)). Treatment response rates were calculated based on a CHQ improvement of at least 1 standard error of measurement. RESULTS: Significant improvements in HRQL were found following both acute and long-term treatment for psychosocial but not physical health. Of participants who completed treatment (n = 312 or 34.2% of those enrolled), 81% responded to acute treatment and 78% responded to long-term treatment. Improvements noted after acute treatment were maintained during long-term treatment with the majority of participants (86%) continuing to respond to treatment. CONCLUSIONS: Atomoxetine is associated with improvements in HRQL, and the improvements are generally stable over time

Emotional expression during attention-deficit/hyperactivity disorders treatment: initial assessment of treatment effects.

OBJECTIVE: The purpose of this research was to provide an initial examination of the effects of atomoxetine and stimulants on emotional expression using a newly developed scale for assessing emotional expression in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: The parent-rated Expression and Emotion Scale for Children (EESC) was collected during two studies. During a cross-sectional validation study, the EESC was completed to assess the child\u27s current treatment and retrospectively for previous medication. In a randomized, placebo-controlled trial of atomoxetine, the EESC was collected at baseline and endpoint. RESULTS: In the validation study, no statistically significant differences in EESC scores were found between groups taking atomoxetine (n = 74) and stimulants (n = 105). Patients who switched from a stimulant to atomoxetine (n = 40) had greater improvement in emotional expression than those switched to another stimulant (n = 21) (p = 0.008). In the clinical trial, no difference in rates of worsening of emotional expression were observed (atomoxetine 8.8%, placebo 12.3%; p = 0.440). CONCLUSION: No treatment differences in emotional expression were observed based on current medications. However, stimulant patients needing to switch medications may have greater improvements in emotional expression by switching to atomoxetine

Structural Atrophy of the Right Superior Frontal Gyrus in Adolescents With Severe Irritability

Severe irritability is common in youths with psychiatric disorders and results in significant dysfunction across domains (academic, social, and familial). Prior structural MRI studies in the pediatric population demonstrated that aberrations of cortical thickness (CT) and gray matter volume (GMV) in the fronto-striatal-temporal regions which have been associated with irritability. However, the directions of the correlations between structural alteration and irritability in the individual indices were not consistent. Thus, we aim to address this by implementing comprehensive assessments of CT, GMV, and local gyrification index (LGI) simultaneously in youths with severe levels of irritability by voxel-based morphometry and surface-based morphometry. One hundred and eight adolescents (46 youths with severe irritability and 62 healthy youths, average age = 14.08 years, standard deviation = 2.36) were scanned with a T1-weighted MRI sequence. The severity of irritability was measured using the affective reactivity index. In youths with severe irritability, there was decreased CT, GMV, and LGI in the right superior frontal gyrus (SFG) compared to healthy youths, and negative correlations between these indices of the SFG and irritability. Our findings suggest that structural deficits in the SFG, potentially related to its role in inhibitory control, may be critical for the neurobiology of irritability

A pilot study of atomoxetine in young children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds. METHOD: Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit. RESULTS: Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p \u3c 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p \u3c 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p \u3c 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children\u27s Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p \u3c 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p \u3c 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy. CONCLUSION: Atomoxetine was generally effective for reducing core ADHD symptoms in the 5 and 6 year olds in this open-label study

Acute atomoxetine treatment of younger and older children with ADHD: A meta-analysis of tolerability and efficacy

<p>Abstract</p> <p>Background</p> <p>Atomoxetine is FDA-approved as a treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years to adult. Among pediatric clinical trials of atomoxetine to date, six with a randomized, double-blind, placebo-controlled design were used in this meta-analysis. The purpose of this article is to describe and compare the treatment response and tolerability of atomoxetine between younger children (6–7 years) and older children (8–12 years) with ADHD, as reported in these six acute treatment trials.</p> <p>Methods</p> <p>Data from six clinical trials of 6–9 weeks duration were pooled, yielding 280 subjects, ages 6–7 years, and 860 subjects, ages 8–12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed ADHD. Efficacy was analyzed using the ADHD Rating Scale-IV (ADHD-RS), Conners' Parent Rating Scale-revised (CPRS-R:S), and the Clinical Global Impression of ADHD Severity (CGI-ADHD-S).</p> <p>Results</p> <p>Atomoxetine was superior to placebo in both age categories for mean (SD) change in ADHD-RS total, total T, and subscale scores; 3 CPRS-R:S subscales; and CGI-ADHD-S from baseline. Although there were no significant treatment differentials between the age groups for these efficacy measures, the age groups themselves, regardless of treatment, were significantly different for ADHD-RS total (younger: ATX = -14.2 [13.8], PBO = -4.6 [10.4]; older: ATX = -15.4 [13.2], PBO = -7.3 [12.0]; p = .001), total T (younger: ATX = -15.2 [14.8], PBO = -4.9 [11.2]; older: ATX = -16.4 [14.6], PBO = -7.9 [13.1]; p = .003), and subscale scores (Inattentive: younger: ATX = -7.2 [7.5], PBO = -2.4 [5.7]; older: ATX = -8.0 [7.4], PBO = -3.9 [6.7]; p = .043; Hyperactive/Impulsive: younger: ATX = -7.0 [7.2], PBO = -2.1 [5.4]; older: ATX = -7.3 [7.0], PBO = -3.4 [6.3]; p < .001), as well as the CGI-ADHD-S score (younger: ATX = -1.2 [1.3], PBO = -0.5 [0.9]; older: ATX = -1.4 [1.3], PBO = -0.7 [1.1]; p = .010). Although few subjects discontinued from either age group due to adverse events, a significant treatment-by-age-group interaction was observed for abdominal pain (younger: ATX = 19%, PBO = 6%; older: ATX = 15%, PBO = 13%; p = .044), vomiting (younger: ATX = 14%, PBO = 2%; older: ATX = 9%, PBO = 6%; p = .053), cough (younger: ATX = 10%, PBO = 6%; older: ATX = 3%, PBO = 9%; p = .007), and pyrexia (younger: ATX = 5%, PBO = 2%; older: ATX = 3%, PBO = 5%; p = .058).</p> <p>Conclusion</p> <p>Atomoxetine is an effective and generally well-tolerated treatment of ADHD in both younger and older children as assessed by three recognized measures of symptoms in six controlled clinical trials.</p> <p>Trial Registration</p> <p>Not Applicable.</p