Acute atomoxetine treatment of younger and older children with ADHD: a meta-analysis of tolerability and efficacy.
BACKGROUND
Atomoxetine is FDA-approved as a treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 years to adult. Among pediatric clinical trials of atomoxetine to date, six with a randomized, double-blind, placebo-controlled design were used in this meta-analysis. The purpose of this article is to describe and compare the treatment response and tolerability of atomoxetine between younger children (6-7 years) and older children (8-12 years) with ADHD, as reported in these six acute treatment trials.


METHODS
Data from six clinical trials of 6-9 weeks duration were pooled, yielding 280 subjects, ages 6-7 years, and 860 subjects, ages 8-12 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-diagnosed ADHD. Efficacy was analyzed using the ADHD Rating Scale-IV (ADHD-RS), Conners' Parent Rating Scale-revised (CPRS-R:S), and the Clinical Global Impression of ADHD Severity (CGI-ADHD-S).


RESULTS
Atomoxetine was superior to placebo in both age categories for mean (SD) change in ADHD-RS total, total T, and subscale scores; 3 CPRS-R:S subscales; and CGI-ADHD-S from baseline. Although there were no significant treatment differentials between the age groups for these efficacy measures, the age groups themselves, regardless of treatment, were significantly different for ADHD-RS total (younger: ATX = -14.2 [13.8], PBO = -4.6 [10.4]; older: ATX = -15.4 [13.2], PBO = -7.3 [12.0]; p = .001), total T (younger: ATX = -15.2 [14.8], PBO = -4.9 [11.2]; older: ATX = -16.4 [14.6], PBO = -7.9 [13.1]; p = .003), and subscale scores (Inattentive: younger: ATX = -7.2 [7.5], PBO = -2.4 [5.7]; older: ATX = -8.0 [7.4], PBO = -3.9 [6.7]; p = .043; Hyperactive/Impulsive: younger: ATX = -7.0 [7.2], PBO = -2.1 [5.4]; older: ATX = -7.3 [7.0], PBO = -3.4 [6.3]; p < .001), as well as the CGI-ADHD-S score (younger: ATX = -1.2 [1.3], PBO = -0.5 [0.9]; older: ATX = -1.4 [1.3], PBO = -0.7 [1.1]; p = .010). Although few subjects discontinued from either age group due to adverse events, a significant treatment-by-age-group interaction was observed for abdominal pain (younger: ATX = 19%, PBO = 6%; older: ATX = 15%, PBO = 13%; p = .044), vomiting (younger: ATX = 14%, PBO = 2%; older: ATX = 9%, PBO = 6%; p = .053), cough (younger: ATX = 10%, PBO = 6%; older: ATX = 3%, PBO = 9%; p = .007), and pyrexia (younger: ATX = 5%, PBO = 2%; older: ATX = 3%, PBO = 5%; p = .058).


CONCLUSIONS
Atomoxetine is an effective and generally well-tolerated treatment of ADHD in both younger and older children as assessed by three recognized measures of symptoms in six controlled clinical trials.


BACKGROUND
Not Applicable.
Kratochvil
Christopher J
CJ
University of Nebraska Medical Center, Nebraska Medical Center, Omaha, NE 68198-5581, USA. ckratoch@unmc.edu
Milton
Denái R
DR
Vaughan
Brigette S
BS
Greenhill
Laurence L
LL
J Am Acad Child Adolesc Psychiatry. 2006 Aug;45(8):919-927
16865034
J Am Acad Child Adolesc Psychiatry. 1998 Jul;37(7):695-702
9666624
J Am Acad Child Adolesc Psychiatry. 2001 May;40(5):508-15
11349694
Arch Gen Psychiatry. 1999 Dec;56(12):1073-86
10591283
J Am Acad Child Adolesc Psychiatry. 2006 Feb;45(2):149-157
16429085
J Am Acad Child Adolesc Psychiatry. 2006 Nov;45(11):1284-1293
17023867
J Am Acad Child Adolesc Psychiatry. 1996 Feb;35(2):204-14
8720630
Am J Psychiatry. 2002 Nov;159(11):1896-901
12411225
J Clin Psychiatry. 2002 Dec;63(12):1140-7
12523874
Pediatrics. 2004 Jul;114(1):e1-8
15231966
Cardiovasc Res. 1997 Jul;35(1):2-3
9302340
J Abnorm Child Psychol. 1998 Dec;26(6):475-94
9915654
J Clin Psychiatry. 2002;63 Suppl 12:44-9
12562061
Am J Psychiatry. 2008 Jun;165(6):721-30
18281409
J Child Adolesc Psychopharmacol. 2007 Apr;17(2):175-85
17489712
J Am Acad Child Adolesc Psychiatry. 2007 Jul;46(7):894-921
17581453