Once-Daily Atomoxetine Treatment for Children With Attention-Deficit/Hyperactivity Disorder, Including an Assessment of Evening and Morning Behavior: A Double-Blind, Placebo-Controlled Trial

Abstract

ABSTRACT. Objectives. Atomoxetine seems to be as effective for treating attention-deficit/hyperactivity disorder (ADHD) when the daily dose is administered once in the morning as when the dose is divided and administered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening and early morning. Another goal was to determine how early in treatment it was possible to discern a specific effect of the drug on ADHD symptoms.Methods. This study was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 12 outpatient sites in the United States. A total of 197 children, 6 to 12 years of age, who had been diagnosed as having ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, were randomized to receive 8 weeks of treatment with atomoxetine or placebo, dosed once daily in the mornings. ADHD symptoms were assessed with parent and investigator rating scales. The primary outcome measure was the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score. Daily parent assessments of children's home behaviors in the evening and early morning were recorded with an electronic data entry system. This instrument measures 11 specific morning or evening activities, including getting up and out of bed, doing or completing homework, and sitting through dinner.Results. Seventy-one percent of the children enrolled were male, 69% met criteria for the combined subtype (both inattentive and hyperactive/impulsive symptoms), and the most common psychiatric comorbidity was oppositional defiant disorder (35%). Once-daily atomoxetine (final mean daily dose of 1.3 mg/kg) was significantly more effective than placebo in treating core symptoms of ADHD. Mean reductions in the AttentionDeficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score were significantly greater for patients randomized to atomoxetine, beginning at the first visit after the initiation of treatment and continuing at all subsequent visits. Both inattentive and hyperactive/impulsive symptom clusters were significantly reduced with atomoxetine, compared with placebo. With continued treatment and dose titrations, core symptoms of ADHD continued to decrease throughout the 8-week study. Mean reductions in the daily parent assessment total scores for patients randomized to atomoxetine were superior during the first week, beginning with the first day of dosing, and were also superior at endpoint. Efficacy outcomes for the evening hours for atomoxetine-treated patients were superior to those for placebo-treated patients, as assessed with 2 different assessment scales. Decreases in the daily parent assessment morning subscores at endpoint showed a significant reduction in symptoms that lasted into the mornings. Rates of discontinuations attributable to adverse events were <5% for...

Efficacy and safety of atomoxetine as add-on to psychoeducation in the treatment of attention deficit/hyperactivity disorder

“…Placebo-treated patients showed very little improvement beyond this 3-week time point. At endpoint, the lsmean decrease in the ADHD-RS score for placebo-treated patients was 6.3 points, a change very similar to that seen in other placebo-controlled atomoxetine trials that did not include concomitant psychoeducation: In five of six placebo-controlled studies, each with a duration of 6-9 weeks and using investigator-rated ADHD-RS, the mean change in the placebo-treated group varied between 5.5 and 7.0 points [11][12][13][14], whereas corresponding decreases in mean ADHD-RS scores in the atomoxetine-treated groups of these studies varied between 12.8 and 16.7 points; however, this was still well below the lsmean reduction of 19.0 points observed in the present study.…”

“…Administered once-daily in the morning, it provides continuous symptom relief that lasts not only into the evening hours but also into the morning hours [11]. Atomoxetine was proven to be a well-tolerated and efficacious treatment for ADHD in the first six acute placebo-controlled studies, in which it was always statistically superior to placebo [11][12][13][14][15]. Currently it presents by far the most extensively studied pharmacotherapeutic drug in clinical trials on children with ADHD [16].…”

A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents

“…No significant differences were detected between treatment groups in the incidence of headache, 63,73,74 stomach ache 63,73,74 or insomnia. 73 However, participants in the ATX treatment groups displayed significant reductions in appetite in two of the three trials (Figure 16).…”

“…Three studies in this category examined hyperactivity and CGI, 63,73,74 with almost all results favouring ATX over placebo. However, the lowest dose of ATX examined (0.5 mg/kg/day) did not significantly improve behaviour when measured using the ADHD Rating Scale or CGI.…”

“…Michelson and colleagues 74 and Kelsey and colleagues 63 both reported improvements in the ATX group compared with placebo ( p < 0.001 and p < 0.05, respectively). Michelson and colleagues 73 observed a significant difference when 1.2 mg/kg/day was administered ( p = 0.002), but not when 0.5 mg/kg/day was administered.…”