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Abstracts Atomoxetina

1.- Once-daily atomoxetine treatment for children and adolescents with

attention deficit hyperactivity disorder: a randomized, placebo-controlled
study

Authors
Michelson D. Allen AJ. Busner J. Casat C. Dunn D. Kratochvil C. Newcorn
J. Sallee FR. Sangal RB. Saylor K. West S. Kelsey D. Wernicke J. Trapp
NJ. Harder D.
Comments
Comment in: Evid Based Ment Health. 2003 May;6(2):42; PMID: 12719349
Source
American Journal of Psychiatry. 159(11):1896-901, 2002 Nov.
Abstract
OBJECTIVE: The authors assessed the efficacy of once-daily atomoxetine
administration in the treatment of children and adolescents with attention
deficit hyperactivity disorder (ADHD). METHOD: In a double-blind study,
children and adolescents with ADHD (N=171, age range=6-16 years) were
randomly assigned to receive 6 weeks of treatment with either atomoxetine
(administered once daily) or placebo. RESULTS: Outcomes among
atomoxetine-treated patients were superior to those of the placebo
treatment group as assessed by investigator, parent, and teacher ratings.
The treatment effect size (0.71) was similar to those observed in previous
atomoxetine studies that used twice-daily dosing. Parent diary ratings
suggested that drug-specific effects were sustained late in the day.
Discontinuations due to adverse events were low (less than 3%) for both
treatment groups, and no serious safety concerns were observed.
CONCLUSIONS: Once-daily administration of atomoxetine is an effective
treatment for children and adolescents with ADHD.

__________________________________________________________________

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2.- Atomoxetine in the treatment of children and adolescents with attention-

deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-
response study

Authors
Michelson D. Faries D. Wernicke J. Kelsey D. Kendrick K. Sallee FR.
Spencer T. Atomoxetine ADHD Study Group.
Source
Pediatrics. 108(5):E83, 2001 Nov.
Abstract
OBJECTIVE: Atomoxetine is an investigational, nonstimulant
pharmacotherapy being studied as potential treatment for attention-
deficit/hyperactivity disorder (ADHD). It is thought to act via blockade of the
presynaptic norepinephrine transporter in the brain. We assessed the
efficacy of 3 doses of atomoxetine compared with placebo in children and
adolescents with ADHD. METHODS: A total of 297 children and
adolescents who were 8 to 18 years of age and had ADHD as defined by
the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, were
randomized to placebo or atomoxetine dosed on a weight-adjusted basis at
0.5 mg/kg/day, 1.2 mg/kg/day, or 1.8 mg/kg/day for an 8-week period.
ADHD symptoms, affective symptoms, and social and family functioning
were assessed using parent and investigator rating scales. RESULTS:
Approximately 71% of children enrolled were male, approximately 67% met
criteria for mixed subtype (both inattentive and hyperactive/impulsive
symptoms), and the only common psychiatric comorbidity was oppositional
defiant disorder (approximately 38% of the sample). At baseline, symptom
severity was rated as moderate to severe for most children. At endpoint,
atomoxetine 1.2 mg/kg/day and 1.8 mg/kg/day were consistently associated
with superior outcomes in ADHD symptoms compared with placebo and
were not different from each other. The dose of 0.5 mg/kg/day was
associated with intermediate efficacy between placebo and the 2 higher
doses, suggesting a graded dose-response. Social and family functioning
also were improved in the atomoxetine groups compared with placebo with
statistically significant improvements in measures of children's ability to
meet psychosocial role expectations and parental impact. Discontinuations
as a result of adverse events were <5% for all groups. CONCLUSION:
Among children and adolescents aged 8 to 18, atomoxetine was superior to
placebo in reducing ADHD symptoms and in improving social and family
functioning symptoms. Atomoxetine was associated with a graded dose-
response, and 1.2 mg/kg/day seems to be as effective as 1.8 mg/kg/day
and is likely to be the appropriate initial target dose for most patients.
Treatment with atomoxetine was safe and well tolerated.
__________________________________________________________________

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3.- An open-label, dose-ranging study of atomoxetine in children with

attention deficit hyperactivity disorder
Authors
Spencer T. Biederman J. Heiligenstein J. Wilens T. Faries D. Prince J.
Faraone SV. Rea J. Witcher J. Zervas S.
Source
Journal of Child & Adolescent Psychopharmacology. 11(3):251-65, 2001
Fall.
Abstract
OBJECTIVE: The goal of this study was to evaluate the tolerability and
effectiveness of the experimental, noradrenergic specific reuptake inhibitor
atomoxetine in the treatment of children with attention deficit hyperactivity
disorder (ADHD). METHODS: This was an open, prospective, dose-ranging
study of atomoxetine monotherapy in the treatment of 30 children with
ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-
20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on
response and adverse effects. Twenty-two children completed the full 11
weeks. We assessed efficacy with weekly clinician and parent ratings of
ADHD and oppositional symptoms and monitored adverse effects,
laboratory findings, and cardiovascular parameters. RESULTS: Treatment
with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very
well tolerated without meaningful adverse effects. Atomoxetine significantly
reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease
vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of
the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of
subjects who completed 10 weeks of treatment showed > 25% decrease in
ADHD symptoms. CONCLUSIONS: These findings extend to children the
positive results previously reported in adults diagnosed with ADHD who
were treated with atomoxetine. These results support additional controlled
trials of atomoxetine in cases of pediatric ADHD.
__________________________________________________________________

4.- An open-label, dose-ranging study of atomoxetine in children with

attention deficit hyperactivity disorder.

Authors
Spencer T. Biederman J. Heiligenstein J. Wilens T. Faries D. Prince J.
Faraone SV. Rea J. Witcher J. Zervas S.
Institution
Pediatric Psychopharmacology Unit, Massachusetts General Hospital,
Boston 02114, USA.
Source
Journal of Child & Adolescent Psychopharmacology. 11(3):251-65, 2001
Fall.
Abstract
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84 39 81

OBJECTIVE: The goal of this study was to evaluate the tolerability and
effectiveness of the experimental, noradrenergic specific reuptake inhibitor
atomoxetine in the treatment of children with attention deficit hyperactivity
disorder (ADHD). METHODS: This was an open, prospective, dose-ranging
study of atomoxetine monotherapy in the treatment of 30 children with
ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-
20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on
response and adverse effects. Twenty-two children completed the full 11
weeks. We assessed efficacy with weekly clinician and parent ratings of
ADHD and oppositional symptoms and monitored adverse effects,
laboratory findings, and cardiovascular parameters. RESULTS: Treatment
with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very
well tolerated without meaningful adverse effects. Atomoxetine significantly
reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease
vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of
the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of
subjects who completed 10 weeks of treatment showed > 25% decrease in
ADHD symptoms. CONCLUSIONS: These findings extend to children the
positive results previously reported in adults diagnosed with ADHD who
were treated with atomoxetine. These results support additional controlled
trials of atomoxetine in cases of pediatric ADHD.
__________________________________________________________________

6.- Atomoxetine: a selective noradrenaline reuptake inhibitor for the

treatment of attention-deficit/hyperactivity disorder. [Review] [31 refs]
Authors
Kratochvil CJ. Vaughan BS. Harrington MJ. Burke WJ.
Institution
Department of Psychiatry, University of Nebraska Medical Center, Omaha
68191-5581, USA. ckratoch@unmc.edu
Source
Expert Opinion on Pharmacotherapy. 4(7):1165-74, 2003 Jul.
Abstract
Atomoxetine (Strattera, Eli Lilly & Co.) is a selective noradrenaline reuptake
inhibitor that has been studied for use in the treatment of attention-
deficit/hyperactivity disorder (ADHD). So far, two open-label and seven
randomised, double-blind, placebo-controlled, clinical trials have been
published, six in youths and three in adults. Each of these trials has shown
a positive response as measured by the primary efficacy measures, the
ADHD-IV Rating Scale (ADHD RS) or the Conners Adult ADHD Rating
Scale (CAARS). Atomoxetine has generally been well tolerated. In
November of 2002 the FDA approved atomoxetine for use in the US for the
treatment of ADHD in children, adolescents and adults. Atomoxetine is the
first nonstimulant approved by the FDA for the treatment of ADHD and the
first medication approved for the treatment of adult ADHD. [References: 31]
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__________________________________________________________________

7.- Atomoxetine pharmacokinetics in children and adolescents with attention

deficit hyperactivity disorder.
Authors
Witcher JW. Long A. Smith B. Sauer JM. Heilgenstein J. Wilens T. Spencer
T. Biederman J.
Source
Journal of Child & Adolescent Psychopharmacology. 13(1):53-63, 2003
Spring.
Abstract
OBJECTIVE: Atomoxetine is indicated for the treatment of attention deficit
hyperactivity disorder in children, adolescents, and adults. This study was
conducted, in part, to evaluate the single-dose and steady-state
pharmacokinetics of atomoxetine in pediatric patients. METHODS: This was
an open-label, dose-titration study in pediatric patients with attention deficit
hyperactivity disorder. Eligible patients could elect to participate in a single-
dose or steady-state discontinuation pharmacokinetic evaluation including
serial plasma sample collection over 24 hours. Plasma concentrations of
atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were
determined using an atmospheric pressure chemical ionization liquid
chromatography/mass spectrometry/mass spectrometry assay.
Pharmacokinetic parameters were calculated using noncompartmental
analysis. RESULTS: Twenty-one cytochrome P450 2D6 extensive
metabolizer patients participated in these single-dose and steady-state
pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak
plasma concentrations occurring 1 to 2 hours after dosing. Half-life
averaged 3.12 and 3.28 hours after a single dose and at steady state,
respectively. Minimal accumulation occurred in plasma after multiple twice-
daily dosing in extensive metabolizer pediatric patients, as expected based
on single-dose pharmacokinetics. As the dose (in mg/kg) increased,
proportional increases in area under the curve were observed.
CONCLUSIONS: The pharmacokinetics of atomoxetine in extensive
metabolizer patients were well characterized over a wide range of doses in
this study. Atomoxetine pharmacokinetics in pediatric patients and adult
subjects were similar after adjustment for body weight.

__________________________________________________________________

8.- Efficacy of atomoxetine versus placebo in school-age girls with attention-

deficit/hyperactivity disorder

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Authors
Biederman J. Heiligenstein JH. Faries DE. Galil N. Dittmann R. Emslie GJ.
Kratochvil CJ. Laws HF. Schuh KJ. Atomoxetine ADHD Study Group.
Institution
Massachusetts General Hospital, Boston, Massachusetts, USA.
Source
Pediatrics. 110(6):e75, 2002 Dec.
Abstract
OBJECTIVE: The efficacy of atomoxetine was assessed in school-age girls
with attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a potent
inhibitor of the presynaptic norepinephrine transporter with minimal affinity
for other noradrenergic receptors or for other neurotransmitter transporters
or receptors. METHODS: A total of 291 children who were 7 to 13 years of
age and met Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition criteria for ADHD participated in 1 of 2 combined, double-blind,
placebo-controlled, multisite, identical clinical trials. This intent-to-treat
subset analysis examined the effects of atomoxetine versus placebo in 51
girls who were randomized to atomoxetine (n = 30) or placebo (n = 21) for 9
weeks. ADHD symptoms were assessed using parent- and investigator-
rated scales. RESULTS: Atomoxetine was superior to placebo on the
following measures: the Attention-Deficit Hyperactivity Disorder Rating
Scale-IV-Parent Version: Investigator Administered and Scored Total Score;
the Inattentive and Hyperactive/Impulsive subscales of the Attention-Deficit
Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator
Administered and Scored Total Score; the ADHD Index subscale of the
Conners' Parent Rating Scale-Revised: Short Form; and the Clinical Global
Impressions of Severity of ADHD. Statistically significant efficacy was seen
1 week after randomization and remained so for the duration of the study.
One patient from each of the atomoxetine and placebo groups discontinued
the study as a result of an adverse event. CONCLUSION: Atomoxetine was
found to be effective and well tolerated for the treatment of ADHD in school-
age girls.

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