Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient, parent and physician perspective using items from the pediatric adverse event rating scale (PAERS)

Child and Adolescent Psychiatry and Mental Health BioMed Central Open Access Research Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient, parent and physician perspective using items from the pediatric adverse event rating scale (PAERS) Peter M Wehmeier*1, Alexander Schacht1, Martin Lehmann1, Ralf W Dittmann1,2, Susan G Silva3 and John S March3 Address: 1Lilly Deutschland, Medical Department, Bad Homburg, Germany, 2Department of Child and Adolescent Psychosomatic Medicine, University of Hamburg, Germany and 3Duke University Child and Family Study Center, Duke University Medical Center, Durham, N.C., USA Email: Peter M Wehmeier* - ; Alexander Schacht - ; Martin Lehmann - ; Ralf W Dittmann - ; Susan G Silva - ; John S March - * Corresponding author Published: 28 May 2008 Child and Adolescent Psychiatry and Mental Health 2008, 2:11 11 doi:10.1186/1753-2000-2- Received: 27 February 2008 Accepted: 28 May 2008 This article is available from: http://www.capmh.com/content/2/1/11 © 2008 Wehmeier et al; licensee BioMed Central Ltd. 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. Abstract Background: The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS) that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician. Methods: Patients aged 6–17 years with ADHD were treated with atomoxetine (target dose 1.2 mg/kg/day). In the two studies on which this secondary analysis is based the PAERS was used to assess the tolerability of atomoxetine in children and adolescents. This scale has a total of 48 items. The ten items that reflect emotional well-being were selected to measure changes over time from a patient, parent, and physician perspective. Results: 421 patients were treated with atomoxetine. 355 patients completed the 8-week treatment period, and 260 patients completed the 24-week treatment period. The ten items that reflect emotional well-being were grouped in five dimensions: depressed mood, self-harm, irritability/agitation, drowsiness, and euphoria. The scores of these dimensions decreased over time, both from a patient as well as from a parent and physician perspective. Only the dimension self-harm was extremely low at baseline and stayed low over time. The mean scores for the ten items depended on the rater perspective. Conclusion: The emotional well-being of children and adolescents with ADHD improved in terms of depressed mood, irritability/agitation, drowsiness, and euphoria during treatment with atomoxetine for up to 24 weeks. Page 1 of 10 (page number not for citation purposes) Child and Adolescent Psychiatry and Mental Health 2008, 2:11 Background Attention-deficit/hyperactivity disorder (ADHD) is a disorder characterized by inattention, impulsivity, and hyperactivity that affects 3–7% of school-age children [1]. ADHD is usually associated with significant impairment of cognitive and psychosocial functioning [2,3] and can have a significant impact on the emotional well-being [46] and the quality of life (QoL) of both patients and their families [7-12]. Psychostimulants and behavioral therapy are known to be effective in the treatment of ADHD, as reported in the MTA study [13]. Atomoxetine is a non-stimulant treatment option for ADHD [14,15], for which efficacy and tolerability in children and adolescents have been demonstrated in a number of randomized, placebo-controlled trials [16-19], supported by a recent meta-analysis [20]. In most of these studies, questionnaires such as the ADHDRating Scale (ADHD-RS) [21,22] or the Clinical Global Impression (CGI) [23,24] have been used as outcome measures for the core symptoms of ADHD. Other questionnaires such as the Child Health Questionnaire (CHQ) [25] or the Child Health and Illness Profile, Child Edition (CHIP-CE) [26] assess aspects of ADHD that go beyond the core symptoms of the disorder and reflect various dimensions of health-related quality of life. However, such questionnaires are often rated by the investigator alone, resulting in an assessment from one perspective only. Therefore, several studies have attempted to compare the perspectives of the various individuals involved, such as the patient, the parent, or the physician, as these perspectives have been shown to differ [12,27]. The newly devised Global Impression of Perceived Difficulties (GIPD) is one such instrument with which the three perspectives can be compared [28,29]. The Pediatric Adverse Event Rating Scale (PAERS) also allows the comparison between patient, parent, and physician perspectives, although it was designed to capture the tolerability of medication rather than efficacy [30]. This report is based on a secondary analysis of data from two almost identical multi-center, single-arm, open-label studies in two different age groups (children and adolescents). These studies were designed to investigate the quality of life in patients with ADHD treated with atomoxetine as reflected by the degree of difficulties perceived by patients, parents and physicians [28,29]. The two studies were undertaken to address the need for further research on evidence-based psychopharmacological treatments in children and adolescents [31]. One of the aims of the two studies on which this post-hoc analysis is based [28,29] was to assess the tolerability of atomoxetine in these patients and compare the tolerability as perceived from the three perspectives (patient, parent, physician) using the Pediatric Adverse Event Rating Scale (PAERS). http://www.capmh.com/content/2/1/11 The PAERS is a 48-item questionnaire designed to assess any type of adverse event occurring in pediatric patients who are treated with psychotropic medication, especially as participant in clinical trials, and was developed as part of the Child and Adolescent Psychiatry Trials Network (CAPTN) [30,32-34]. The response captures the severity of 48 adverse event items on a five-point Likert scale (0–4). The main assumption of this post-hoc analysis was that 10 of the 48 items of the PAERS are directly related to the patients' emotional state and can therefore be considered to reflect the patient's emotional well-being. Based on this assumption, the hypothesis of this analysis was that the emotional well-being of children and adolescents with ADHD responds well to treatment with atomoxetine as reflected by the 10 items of the PAERS directly related to the patient's emotional state. Differences between the three perspectives (patient, parent, physici (...truncated)