This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kelsey, D. K. Articles by Allen, A. J. Search for Related Content PubMed PubMed Citation Articles by Kelsey, D. K. Articles by Allen, A. J. Related Collections Neurology & Psychiatry Social Bookmarking                         What's this?

PEDIATRICS Vol. 114 No. 1 July 2004, pp. e1-e8

ELECTRONIC ARTICLE

Once-Daily Atomoxetine Treatment for Children With Attention-Deficit/Hyperactivity Disorder, Including an Assessment of Evening and Morning Behavior: A Double-Blind, Placebo-Controlled Trial

Douglas K. Kelsey, MD, PhD^*, Calvin R. Sumner, MD^*, Charles D. Casat, MD, Daniel L. Coury, MD, Humberto Quintana, MD^||, Keith E. Saylor, PhD^¶, Virginia K. Sutton, PhD^*, Jill Gonzales, BS^*, Sandra K. Malcolm, BS^*, Kory J. Schuh, PhD^* and Albert J. Allen, MD, PhD^*

^* Lilly Research Laboratories, Indianapolis, Indiana
Behavioral Health Center, Charlotte, North Carolina
Children's Hospital, Pediatric Clinical Trials International, Columbus, Ohio
^|| Louisiana State University Health Science Center, New Orleans, Louisiana
^¶ NeuroScience, Inc, Bethesda, Maryland

Objectives. Atomoxetine seems to be as effective for treating attention-deficit/hyperactivity disorder (ADHD) when the daily dose is administered once in the morning as when the dose is divided and administered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening and early morning. Another goal was to determine how early in treatment it was possible to discern a specific effect of the drug on ADHD symptoms.

Methods. This study was a randomized, multicenter, double-blind, placebo-controlled trial conducted at 12 outpatient sites in the United States. A total of 197 children, 6 to 12 years of age, who had been diagnosed as having ADHD, on the basis of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, were randomized to receive 8 weeks of treatment with atomoxetine or placebo, dosed once daily in the mornings. ADHD symptoms were assessed with parent and investigator rating scales. The primary outcome measure was the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score. Daily parent assessments of children's home behaviors in the evening and early morning were recorded with an electronic data entry system. This instrument measures 11 specific morning or evening activities, including getting up and out of bed, doing or completing homework, and sitting through dinner.

Results. Seventy-one percent of the children enrolled were male, 69% met criteria for the combined subtype (both inattentive and hyperactive/impulsive symptoms), and the most common psychiatric comorbidity was oppositional defiant disorder (35%). Once-daily atomoxetine (final mean daily dose of 1.3 mg/kg) was significantly more effective than placebo in treating core symptoms of ADHD. Mean reductions in the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored total score were significantly greater for patients randomized to atomoxetine, beginning at the first visit after the initiation of treatment and continuing at all subsequent visits. Both inattentive and hyperactive/impulsive symptom clusters were significantly reduced with atomoxetine, compared with placebo. With continued treatment and dose titrations, core symptoms of ADHD continued to decrease throughout the 8-week study. Mean reductions in the daily parent assessment total scores for patients randomized to atomoxetine were superior during the first week, beginning with the first day of dosing, and were also superior at endpoint. Efficacy outcomes for the evening hours for atomoxetine-treated patients were superior to those for placebo-treated patients, as assessed with 2 different assessment scales. Decreases in the daily parent assessment morning subscores at endpoint showed a significant reduction in symptoms that lasted into the mornings. Rates of discontinuations attributable to adverse events were <5% for both groups. Adverse events reported significantly more frequently with atomoxetine were decreased appetite, somnolence, and fatigue.

Conclusions. Among children 6 to 12 of age who had been diagnosed as having ADHD, once-daily administration of atomoxetine in the morning provided safe, rapid, continuous, symptom relief that lasted not only into the evening hours but also into the morning hours. Atomoxetine treatment was safe and well tolerated.

---

Key Words: atomoxetine • ADHD • children • continuous relief • once-daily • rapid onset of action

Abbreviations: ADHD, attention-deficit/hyperactivity disorder • GIPE, Global Index: Parent-Evening • ADHD RS, Attention-Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version: Investigator-Administered and Scored • ECG, electrocardiogram • LOCF, last observation carried forward • CGI-ADHD-S, Clinical Global Impressions-Attention-Deficit/Hyperactivity Disorder-Severity • CI, confidence interval • ANCOVA, analysis of covariance • DPREMB-R, Daily Parent Ratings of Evening and Morning Behavior-Revised

---

Received for publication Feb 24, 2003; Accepted Mar 1, 2004.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				W. Weber, A. Vander Stoep, R. L. McCarty, N. S. Weiss, J. Biederman, and J. McClellan Hypericum perforatum (St John's Wort) for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Randomized Controlled Trial JAMA, June 11, 2008; 299(22): 2633 - 2641. [Abstract] [Full Text] [PDF]

				V. Sung, H. Hiscock, E. Sciberras, and D. Efron Sleep Problems in Children With Attention-Deficit/Hyperactivity Disorder: Prevalence and the Effect on the Child and Family Arch Pediatr Adolesc Med, April 1, 2008; 162(4): 336 - 342. [Abstract] [Full Text] [PDF]

				T. J. Spencer, F. R. Sallee, D. L. Gilbert, D. W. Dunn, J. T. McCracken, B. J. Coffey, C. L. Budman, R. K. Ricardi, H. L. Leonard, A. J. Allen, et al. Atomoxetine Treatment of ADHD in Children With Comorbid Tourette Syndrome J Atten Disord, January 1, 2008; 11(4): 470 - 481. [Abstract] [PDF]

				S. V. Faraone, S. B. Wigal, and P. Hodgkins Forecasting Three-Month Outcomes in a Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR) and Atomoxetine (Strattera) in School-Aged Children With ADHD J Atten Disord, July 1, 2007; 11(1): 74 - 82. [Abstract] [PDF]

				A. P Gibson, T. L Bettinger, N. C Patel, and M L. Crismon Atomoxetine Versus Stimulants for Treatment of Attention Deficit/Hyperactivity Disorder Ann. Pharmacother., June 1, 2006; 40(6): 1134 - 1142. [Abstract] [Full Text] [PDF]

				M. D. Rappley Attention Deficit-Hyperactivity Disorder N. Engl. J. Med., January 13, 2005; 352(2): 165 - 173. [Full Text] [PDF]

				J. G. Millichap Effectiveness of Atomoxetine for ADHD AAP Grand Rounds, October 1, 2004; 12(4): 43 - 44. [Full Text] [PDF]