Calvin Russell Sumner

Improvement in health-related quality of life in children with ADHD: an analysis of placebo controlled studies of atomoxetine.

ABSTRACT. Despite significant functional impairments associated with attention-deficit hyperactivity disorder (ADHD) and the growing appreciation of the importance of health-related quality of life (HRQL) assessment in children with chronic disorders, relatively few studies have examined the impact of ADHD treatment on HRQL. This investigation examines the effect of atomoxetine, a nonstimulant treatment for ADHD, on HRQL and identifies factors that are predictive of HRQL improvements. The Child Health Questionnaire (CHQ), which is a multidimensional HRQL measure, was collected during three randomized, double-blind, placebo-controlled clinical trials. Children who received atomoxetine had significantly greater improvement in psychosocial functioning compared to the placebo group. No significant differences between once-a-day and twice-a-day dosing were found. Treatment with atomoxetine, lower HRQL baseline score, no history of stimulant use, and absence of oppositional defiant disorder were all associated with improvements in psychosocial functioning. Findings demonstrate the positive impact of atomoxetine on HRQL in children with ADHD.

Clinical Responses to Atomoxetine in Attention-Deficit/Hyperactivity Disorder: The Integrated Data Exploratory Analysis (IDEA) Study.

OBJECTIVE Clinical experience suggests that some (but not all) patients with attention-deficit/hyperactivity disorder (ADHD) are highly responsive to the nonstimulant atomoxetine. We conducted a retrospective analysis of randomized controlled trials (RCTs) to identify potential baseline (moderator) and on-treatment (mediator) predictors of responses. METHOD Data from 6 U.S. RCTs among patients aged 6 to 18 years were pooled (N = 1,069; subjects treated with atomoxetine, n = 618). Subjects were categorized as much improved (> or = 40% decrease in ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored total score), minimally improved (25%-< 40% decline), or nonresponders (< 25% decrease). Logistic regression, analyses of variance, and repeated-measures analyses were used to explore associations between baseline and on-treatment variables, achieving a much improved response at trial endpoint (6-9 weeks). RESULTS Forty-seven percent of patients showed a much improved clinical response, and 40% did not respond. Only 13% of the patients had a minimal response. No baseline characteristics predicted achieving a much improved clinical response; the only predictor of achieving this response was being at least minimally improved by treatment week 4 (sensitivity = 81%, specificity = 72%, positive predictive value = 75%, and negative predictive value = 79%). CONCLUSIONS Clinical response to atomoxetine was bimodal, with most subjects being either responders who were much improved or nonresponders. There were no demographic or clinical predictors of response. However, subjects who ultimately achieved a much improved response were likely to be at least minimal responders by week 4. The recommendation to consider either augmenting or switching treatment in patients who do not achieve at least this level of response to atomoxetine by 4 weeks offers a method for limiting the extended duration of titration to subjects who are most likely to benefit further, while minimizing the duration of exposure in those less likely to achieve an excellent response.

Once-Daily Atomoxetine for Treating Pediatric Attention-Deficit/Hyperactivity Disorder: Comparison of Morning and Evening Dosing

In this 3-arm, randomized, double-blind trial, once-daily morning-dosed atomoxetine, evening-dosed atomoxetine, and placebo were compared for treating pediatric attention-deficit/hyperactivity disorder (ADHD). Patients received morning atomoxetine/evening placebo (n = 102), morning placebo/evening atomoxetine (n = 93), or morning placebo/evening placebo (n = 93) for about 6 weeks. Core symptom efficacy was measured at weeks 0, 1, 3, and 6. Parent assessments of the child’s home behaviors in the evening and early morning were collected daily during the first 2 weeks of treatment. Morning-dosed and evening-dosed atomoxetine significantly decreased core ADHD symptoms relative to placebo and produced symptom improvements that were measured up to 24 hours later. Morning dosing was superior to evening dosing on some efficacy measures. Evening dosing showed greater tolerability with significantly more patients receiving morning atomoxetine reporting at least 1 adverse event than those receiving evening atomoxetine.

Atomoxetine for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children with ADHD and dyslexia

BackgroundThe objective of this study was to assess the effects of atomoxetine on treating attention-deficit/hyperactivity disorder (ADHD), on reading performance, and on neurocognitive function in youth with ADHD and dyslexia (ADHD+D).MethodsPatients with ADHD (n = 20) or ADHD+D (n = 36), aged 10-16 years, received open-label atomoxetine for 16 weeks. Data from the ADHD Rating Scale-IV (ADHDRS-IV), Kaufman Test of Educational Achievement (K-TEA), Working Memory Test Battery for Children (WMTB-C), and Life Participation Scale for ADHD-Child Version (LPS-C) were assessed.ResultsAtomoxetine demonstrated significant improvement for both groups on the ADHDRS-IV, LPS-C, and K-TEA reading comprehension standard and composite scores. K-TEA spelling subtest improvement was significant for the ADHD group, whereas the ADHD+D group showed significant reading decoding improvements. Substantial K-TEA reading and spelling subtest age equivalence gains (in months) were achieved for both groups. The WMTB-C central executive score change was significantly greater for the ADHD group. Conversely, the ADHD+D group showed significant phonological loop score enhancement by visit over the ADHD group. Atomoxetine was well tolerated, and commonly reported adverse events were similar to those previously reported.ConclusionsAtomoxetine reduced ADHD symptoms and improved reading scores in both groups. Conversely, different patterns and magnitude of improvement in working memory component scores existed between ADHD and ADHD+D patients. Though limited by small sample size, group differences in relation to the comparable changes in improvement in ADHD symptoms could suggest that brain systems related to the therapeutic benefit of atomoxetine in reducing ADHD symptoms may be different in individuals with ADHD+D and ADHD without dyslexia.Trial RegistrationClinical Trial Registry: ClinicalTrials.gov: NCT00191048

Does Placebo Response Differ between Objective and Subjective Measures in Children with Attention-Deficit/Hyperactivity Disorder?

Abstract Placebo response complicates the interpretation of treatment response in both clinical practice and clinical trials in youth with attention-deficit/hyperactivity disorder (ADHD). In a pilot study comparing subjective ADHD symptom rating scales with scores obtained using the Quotient™ ADHD System (an objective computerized technology for assessment of hyper-activity, inattention, and impulsivity in ADHD), it was found that agreement between these 2 measures was not as strong as anticipated. This observation prompted us to evaluate placebo responses associated with subjective and objective assessments. Eligible study participants aged 6 to 14 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD diagnosis based on clinician interviews were randomized to 1 of 2 treatment sequence groups (placebo, low dose, and medium dose; or low dose, medium dose, and placebo) using either atomoxetine HCl or osmotic controlled-release (OROS) methylphenidate HCl as the active treatment in a 3-week, triple-blind (subject, parent, rater) trial. Subjects were exposed to placebo and different medication doses to evaluate the comparative sensitivity of objective and subjective measures in assessing changes in clinical condition. Placebo response was defined using 3 thresholds: any improvement, > 25% improvement, or > 40% improvement from baseline on Quotient™ Global Scaled Score (QGSS) or the ADHD Rating Scale (ADHD-RS) Total score from baseline to the visit when placebo was administered. Lins concordance correlation coefficient was used to measure agreement between baseline and placebo scores for the objective and subjective assessments. Of 30 subjects with placebo and baseline scores, 80%, 47%, and 27% met the 3 response thresholds (ie, any, > 25%, or > 40% improvement, respectively) on the ADHD-RS Total score compared with 27%, 7%, and 0% on the QGSS. Lins concordance correlation coefficient was 0.81 and 0.39 for the QGSS and the ADHD-RS Total score, respectively. Although larger trials are warranted, we tentatively conclude that using objective measures and higher response thresholds may enhance assay sensitivity in clinical trials and hence limit necessary patient enrollments to rule out type II statistical error.

Effects of atomoxetine on attention-deficit/hyperactivity disorder in clinical pediatric treatment settings: a naturalistic study

ABSTRACT Background: Observational studies involving atomoxetine hydrochloride in the treatment of attention-deficit/hyperactivity disorder (ADHD) complement randomized controlled trials by assessing treatment effects in a usual-care setting and including a more heterogeneous patient population. Objective: To provide data on the effectiveness of atomoxetine in a naturalistic treatment setting according to both physician and parent ratings. Design and methods: A prospective, observational (non-interventional), longitudinal, open-label study of patients (N = 627; mean age = 11 years) with ADHD (from 60 physicians’ offices in the United States and Puerto Rico) whose physicians had decided to prescribe atomoxetine either as initial treatment or after trying another ADHD treatment (e.g., stimulants, antidepressants). Patients with a baseline visit and one post-baseline visit for up to 1 year were eligible. Atomoxetine administration, dosing, and timing of follow-up visits were at each physicians discretion. Physicians evaluated the effectiveness of atomoxetine using a single-item rating scale: the Physician Global Impression: ADHD Severity (PGI-ADHD-S) scale. Results: The average reported duration of treatment was 21.2 (range 0–89) weeks. Over this period, treatment significantly lowered ADHD severity compared with baseline, with a mean change of –0.91 (95% confidence interval: –1.00 to –0.82; p < 0.001) on the PGI-ADHD-S scale. Physician-rated improvement was more marked in patients with more severe ADHD at baseline ( p < 0.001). Most patients (59–69%) experienced consistent symptom control at all times of the day. ADHD severity was improved similarly in patients across comorbid conditions (e.g., anxiety, depression, learning disorders), chief complaints (e.g., school problems, emotional problems), and prior treatment with stimulants or other medications. By parent reports, 49% of patients had improved grades following atomoxetine therapy while 35% stayed the same, and improvement in behavior (according to parents’ ratings) occurred in 49% of patients following atomoxetine therapy, whereas 31% stayed the same. Conclusion: Data captured in this study support the conclusion that atomoxetine was effective in reducing symptom severity, and improving progress toward treatment goals, in children and adolescents with ADHD treated in a naturalistic treatment setting. However, given the open-label, observational (non-interventional) design of this study, certain biases cannot be excluded.