A randomized, double-blind, placebo-controlled study of atomoxetine in Japanese children and adolescents with attention-deficit/hyperactivity disorder.
ABSTRACT Until the recent approval of methylphenidate (MPH), Japan had no approved treatment for attention-deficit/hyperactivity disorder (ADHD). The need still exists for an effective, safe, nonstimulant treatment. This first placebo-controlled Japan study of an ADHD nonstimulant therapy assessed atomoxetine efficacy and safety to determine the optimal dose for controlling ADHD symptoms in children and adolescents.
A total of 245 Japanese children and adolescents, aged 6-17 years and diagnosed with ADHD, were randomly assigned to receive placebo or one of three atomoxetine doses (0.5, 1.2, and 1.8 mg/kg per day) over 8 weeks. Symptoms were assessed with the Japanese Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator scored and integrated with teacher reports (ADHD RS-IV-J:I/Sch). Adverse events, vital signs, laboratory tests, and electrocardiograms (ECGs) were obtained for safety analysis.
In all, 234 patients completed the study. Atomoxetine at 1.8 mg/kg per day was significantly superior to placebo in reducing ADHD symptoms (p = 0.01; one-sided). Decreased appetite and vomiting were significantly greater in the atomoxetine treatment groups; however, no clinically significant differences were observed. Two patients discontinued due to affect lability and headache. A linear dose-response and vital signs similar to those from other atomoxetine studies were observed.
Atomoxetine provides an effective and safe nonstimulant option for the treatment of Japanese pediatric patients with ADHD.
Article: A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): rationale and design.[show abstract] [hide abstract]
ABSTRACT: The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study. Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo. The methodology for the ACTION study has been detailed. The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment. Australian and New Zealand Clinical Trials Registry ANZCTRN12607000535471.Trials 03/2011; 12:77. · 2.02 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability.BMC Medicine 06/2011; 9:72. · 6.03 Impact Factor
Article: A randomized, open-label assessment of response to various doses of atomoxetine in korean pediatric outpatients with attention-deficit/hyperactivity disorder.[show abstract] [hide abstract]
ABSTRACT: This multicenter, randomized, open-label, parallel trial aimed to provide a detailed dose-response profile for atomoxetine in Korean pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD). Male and female outpatients aged 6-18 years with ADHD meeting symptom severity criteria of 1.5 standard deviations above age and gender norms on the ADHD Rating Scale-IV-Parent: Investigator-Administered and Scored (ADHDRS-IV-Parent: Inv), and a Clinical Global Impression-ADHD-Severity score ≥4 were randomized to atomoxetine (mg/kg/day) 0.2 fixed, 0.5 fixed or 0.5 (7 days), 0.8 (7 days) then 1.2 for 28 days. The primary efficacy measure was change in ADHDRS-IV-Parent: Inv total score after 6 weeks of atomoxetine treatment. Of 153 randomized patients, 83.7% were male and mean age was 9.8 (SD±2.4) years. The completion rate was 86.9%. A graded dose response was apparent with mean change in ADHDRS-IV-Parent: Inv total scores of -9.6, -12.3 and -14.5 with atomoxetine 0.2, 0.5 and 1.2 mg/kg/day, respectively (p=0.024 - F-test). Moreover, a greater reduction in ADHD symptoms, as assessed by mean change from baseline to endpoint CGI-S and mean CGI-ADHD-Improvement at endpoint, was also observed with increasing atomoxetine dose. More patients receiving atomoxetine 1.2 mg/kg/day reported ≥1 treatment-emergent adverse event/s (58.3%) compared with 0.5 (40.7%; p=0.11) or 0.2 mg/kg/day (29.4%; p=0.005). These were generally mild to moderate. Atomoxetine was found to be safe and well tolerated at all doses administered in Korean pediatric ADHD patients, and 1.2 mg/kg/day was an efficacious dose in this population.Psychiatry investigation 06/2011; 8(2):141-8. · 0.99 Impact Factor