Atomoxetine hydrochloride in the treatment of children and adolescents with attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder: A placebo-controlled Italian study.
OBJECTIVE
The primary aim of this study was to assess the efficacy of atomoxetine in improving ADHD and ODD symptoms in paediatric patients with ADHD and comorbid oppositional defiant disorder (ODD), non-responders to previous psychological intervention with parent support.


METHODS
This was a multicentre, randomised, placebo-controlled trial conducted in patients aged 6-15 years, with ADHD and ODD diagnosed according to the DSM-IV criteria by a structured clinical interview (K-SADS-PL). Only subjects who are non-responders to a 6-week standardized parent training were randomised to atomoxetine (up to 1.2 mg/kg/day) or placebo (in a 3:1 ratio) for the following 8-week double blind phase.


RESULTS
Only 2 of the 156 patients enrolled for the parent support phase (92.9% of males; mean age: 9.9 years), improved after the parent training program; 139 patients were randomised for entering in the study and 137 were eligible for efficacy analysis. At the end of the randomised double blind phase, the mean changes in the Swanson, Nolan and Pelham Rating Scale-Revised (SNAP-IV) ADHD subscale were -8.1+/-9.2 and -2.0+/-4.7, respectively in the atomoxetine and in the placebo group (p<0.001 between groups); changes in the ODD subscale were -2.7+/-4.1 and -0.3+/-2.6, respectively in the two groups (p=0.001 between groups). The CGI-ADHD-S score decreased in the atomoxetine group (median change at endpoint: -1.0) compared to no changes in the placebo group (p<0.001 between groups). Statistically significant differences between groups, in favour of atomoxetine, were found in the CHIP-CE scores for risk avoidance domain, emotional comfort and individual risk avoidance subdomains. An improvement in all the subscales of Conners Parents (CPRS-R:S) and Teacher (CTRS-R:S) subscales was observed with atomoxetine, except in the cognitive problems subscale in the CTRS-R:S. Only 3 patients treated with atomoxetine discontinued the study due to adverse events. No clinically significant changes of body weight, height and vital signs were observed in both groups.


CONCLUSIONS
Treatment with atomoxetine of children and adolescents with ADHD and ODD, who did not initially respond to parental support, was associated with improvements in symptoms of ADHD and ODD, and general health status. Atomoxetine was well tolerated.
Dell'Agnello
Grazia
G
Medical Department, Eli Lilly Italia, Italy.
Maschietto
Dino
D
Bravaccio
Carmela
C
Calamoneri
Filippo
F
Masi
Gabriele
G
Curatolo
Paolo
P
Besana
Dante
D
Mancini
Francesca
F
Rossi
Andrea
A
Poole
Lynne
L
Escobar
Rodrigo
R
Zuddas
Alessandro
A
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D011437:Propylamines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride