Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naïve children and adolescents with attention deficit/hyperactivity disorder.

Abstract

OBJECTIVE:

To test the hypothesis that first-line treatment with atomoxetine provides superior efficacy than placebo for up to 12 weeks in improving the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD).

RESEARCH DESIGN AND METHODS:

This double-blind, randomized, placebo-controlled, parallel clinical trial included 151 treatment-naïve children (n = 113) and adolescents (n = 38) with newly diagnosed (< or =3 months) ADHD. Atomoxetine dose was uptitrated from 0.5 to 1.2 mg/kg/day after two weeks. Outcome assessments included the ADHD Rating Scale-IV-Parent-reported Investigator-rated (ADHDRS-IV-Parent:Inv), the Clinical Global Impression of Severity of ADHD (CGI-ADHD-S), and the incidence of adverse events. Mixed-model repeated measures analysis was used to compare scale score changes between groups.

CLINICAL TRIAL REGISTRATION:

Trial registered at www.clinicaltrials.gov (study internal code: B4Z-XM-LYDM, identifier: NCT00191945).

RESULTS:

Most patients were male (79.2%), of caucasian origin (96.0%) and severely ill (72.5%). Their mean age was 10.3 years. Atomoxetine-treated patients showed greater reductions from baseline to week 12 of total ADHDRS-IV-Parent:Inv score than placebo-treated patients (least square mean difference: -7.9 [95% CI: -11.0 to -4.8], corresponding to a large effect size of 0.8). Between-group mean differences increased progressively with treatment exposure from week 6 to 12 (-2.7 [-4.9 to -0.6] for total and -1.6 [-2.9 to -0.3] for inattention scores). At the end of the study, 50% of atomoxetine-treated patients (14% with placebo) showed a reduction > or =40% in total ADHDRS-IV-Parent:Inv score, and only 29% (46% with placebo) were severely ill (by CGI-ADHD-S). Treatment-related adverse events were significantly more frequent with atomoxetine (65.0%) than with placebo (37.3%), the most frequent being decreased appetite and somnolence. Only one case of decreased appetite was rated as severe. No patient discontinued treatment because of adverse events.

CONCLUSIONS:

A continued improvement of symptoms is expectable until 12 weeks in treatment-naïve ADHD patients treated with atomoxetine as first-line medication. Chief limitations are the small, national sample size and the absence of data beyond the 12-week time-point.

• Authors: Alonso Montoya, Amaia Hervas, Esther Cardo, Josep Artigas, María J Mardomingo, José A Alda, Xavier Gastaminza, María J García-Polavieja, Inmaculada Gilaberte, Rodrigo Escobar
• Journal: Current medical research and opinion (Curr Med Res Opin) Vol. 25 Issue 11 Pg. 2745-54 (Nov 2009) ISSN: 1473-4877 [Electronic] England
• PMID: 19785510 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Uptake Inhibitors
• Placebos
• Propylamines
• Atomoxetine Hydrochloride

Topics

• Adolescent
• Adrenergic Uptake Inhibitors (therapeutic use)
• Age of Onset
• Algorithms
• Atomoxetine Hydrochloride
• Attention Deficit Disorder with Hyperactivity (diagnosis, drug therapy, epidemiology)
• Child
• Double-Blind Method
• Female
• Humans
• Male
• Placebos
• Propylamines (therapeutic use)