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

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          Abstract

          Background

          The 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).

          Methods

          Patients 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.

          Results

          Atomoxetine 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.

          Conclusions

          Atomoxetine 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 Registration

          Clinical Trial Registry: ClinicalTrials.gov: NCT00191048

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          Most cited references9

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          Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study.

          D Michelson, D Faries, J. Wernicke … (2001)
          Atomoxetine is an investigational, nonstimulant pharmacotherapy being studied as potential treatment for attention-deficit/hyperactivity disorder (ADHD). It is thought to act via blockade of the presynaptic norepinephrine transporter in the brain. We assessed the efficacy of 3 doses of atomoxetine compared with placebo in children and adolescents with ADHD. A total of 297 children and adolescents who were 8 to 18 years of age and had ADHD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, were randomized to placebo or atomoxetine dosed on a weight-adjusted basis at 0.5 mg/kg/day, 1.2 mg/kg/day, or 1.8 mg/kg/day for an 8-week period. ADHD symptoms, affective symptoms, and social and family functioning were assessed using parent and investigator rating scales. Approximately 71% of children enrolled were male, approximately 67% met criteria for mixed subtype (both inattentive and hyperactive/impulsive symptoms), and the only common psychiatric comorbidity was oppositional defiant disorder (approximately 38% of the sample). At baseline, symptom severity was rated as moderate to severe for most children. At endpoint, atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated with superior outcomes in ADHD symptoms compared with placebo and were not different from each other. The dose of 0.5 mg/kg/day was associated with intermediate efficacy between placebo and the 2 higher doses, suggesting a graded dose-response. Social and family functioning also were improved in the atomoxetine groups compared with placebo with statistically significant improvements in measures of children's ability to meet psychosocial role expectations and parental impact. Discontinuations as a result of adverse events were <5% for all groups. Among children and adolescents aged 8 to 18, atomoxetine was superior to placebo in reducing ADHD symptoms and in improving social and family functioning symptoms. Atomoxetine was associated with a graded dose-response, and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day and is likely to be the appropriate initial target dose for most patients. Treatment with atomoxetine was safe and well tolerated.
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            Working memory impairments in children with attention-deficit hyperactivity disorder with and without comorbid language learning disorders.

            Rhonda Martinussen, Rosemary Tannock (2006)
            Our objectives were to examine whether children with attention-deficit hyperactivity disorder (ADHD) are impaired on one or more components of working memory (WM) independent of comorbid language learning disorders, and whether WM impairments are more strongly related to symptoms of inattention than to symptoms of hyperactivity-impulsivity. Four groups of children participated: ADHD (n = 62); ADHD+RD/LI (n = 32); RD/LI (n = 15); and a typically developing comparison group (n = 34). Four simple and brief measures of WM were used that varied in modality (auditory-verbal; visual-spatial) and processing demands (temporary storage versus manipulation of information). Children with ADHD without comorbid language learning disorders exhibited deficits in visual-spatial storage and verbal and visual-spatial central executive (C.E.) functions that were independent of comorbid psychiatric disorders. Children with language learning disorders, regardless of comorbidity with ADHD, exhibited impairments in both verbal and spatial storage as well as C.E. domains of WM. Symptoms of inattention, but not symptoms of hyperactivity/impulsivity, predicted performance on verbal and visual-spatial C.E. measures independent of age, verbal cognitive ability, and reading and language performance. Findings are consistent with data implicating neuropsychological impairments in ADHD. The dimensional results are also consistent with prior research demonstrating the neuropsychological impairments are more strongly associated with the inattention symptom dimension than with the hyperactive-impulsive dimension.
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              Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study.

              Peter J. Allen, David Dunn, Joachim Wernicke … (2002)
              The authors assessed the efficacy of once-daily atomoxetine administration in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). In a double-blind study, children and adolescents with ADHD (N=171, age range=6-16 years) were randomly assigned to receive 6 weeks of treatment with either atomoxetine (administered once daily) or placebo. Outcomes among atomoxetine-treated patients were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings. The treatment effect size (0.71) was similar to those observed in previous atomoxetine studies that used twice-daily dosing. Parent diary ratings suggested that drug-specific effects were sustained late in the day. Discontinuations due to adverse events were low (less than 3%) for both treatment groups, and no serious safety concerns were observed. Once-daily administration of atomoxetine is an effective treatment for children and adolescents with ADHD.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Child Adolesc Psychiatry Ment Health
                Title: Child and Adolescent Psychiatry and Mental Health
                Publisher: BioMed Central
                ISSN (Electronic): 1753-2000
                Publication date Collection: 2009
                Publication date (Electronic): 15 December 2009
                Volume: 3
                Page: 40
                Affiliations
                [1 ]Lilly USA, LLC, IN, USA
                [2 ]Department of Psychology, University of York, Heslington, UK
                [3 ]Capstone Clinical Research, Libertyville, IL, USA
                [4 ]Vermont Clinical Study Center, Burlington, VT, USA
                Article
                Publisher ID: 1753-2000-3-40
                DOI: 10.1186/1753-2000-3-40
                PMC ID: 2805604
                PubMed ID: 20003507
                SO-VID: 95d0f20c-9d6a-46e5-8ecf-46c4868e6fc5
                Copyright © Copyright ©2009 Sumner et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 July 2009
                Date accepted : 15 December 2009
                Categories
                Subject: Research

                ScienceOpen disciplines: Clinical Psychology & Psychiatry
                Data availability:
                ScienceOpen disciplines: Clinical Psychology & Psychiatry

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