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


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.


BACKGROUND
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.
Clinical Research, Lilly Research Laboratories, Avenida Industria 30, Alcobendas, Spain.
Alonso
A
Montoya
Amaia
A
Hervas
Esther
E
Cardo
Josep
J
Artigas
María J
MJ
Mardomingo
José A
JA
Alda
Xavier
X
Gastaminza
María J
MJ
García-Polavieja
Inmaculada
I
Gilaberte
Rodrigo
R
Escobar
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D017668:Age of Onset; D000465:Algorithms; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D011437:Propylamines / Q000627:therapeutic use*
D018759:Adrenergic Uptake Inhibitors; D010919:Placebos; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride