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Atomoxetine Treatment in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder and Comorbid Oppositional Defiant Disorder

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ABSTRACT

Objective:

To examine (1) moderating effects of oppositional defiant disorder (ODD) on attention-deficit/hyperactivity disorder (ADHD) treatment response and (2) responses of ODD symptoms to atomoxetine.

Method:

Children and adolescents (ages 8-18) with ADHD were treated for approximately 8 weeks with placebo or atomoxetine (fixed dosing: 0.5, 1.2, or 1.8 mg/kg/day, b.i.d.) under randomized, double-blind conditions. Among patients with lifetime diagnostic information (n = 293), 39% were diagnosed with comorbid ODD and 61% were not. Treatment-group differences and differences between patients with and without comorbid ODD were examined post hoc for changes on the Attention-Deficit/Hyperactivity Disorder Rating Scale IV-Parent version, investigator-administered and -scored; Conners' Parent Rating Scale-Revised Short Form; Clinical Global Impressions Severity of ADHD Scale; and the parent-rated Child Health Questionnaire.

Results:

Youths with ADHD and comorbid ODD showed statistically significant improvement in ADHD, ODD, and quality-of-life measures. Treatment response was similar in youths with and without ODD, except that the comorbid group showed improvement compared with placebo at 1.8 mg/kg/day but not 1.2 mg/kg/day. In contrast, youths without ODD showed improvement at 1.2 mg/kg/day and no incremental benefit at 1.8 mg/kg/day.

Conclusions:

Atomoxetine treatment improves ADHD and ODD symptoms in youths with ADHD and ODD, although the comorbid group may require higher doses.

Section snippets

Patient Sample

This study was conducted at 13 outpatient investigative sites in the United States. Patients were children and adolescents, 8 to 18 years of age, who met DSM-IV (American Psychiatric Association, 2000) criteria for ADHD by clinical assessment and confirmed by structured interview (behavioral module of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime versions (K-SADS-PL) (Kaufman et al., 1997). Patients were also required to have a symptom

Descriptive Characteristics of Youths With ADHD With and Without ODD

Of 297 children and adolescents randomly assigned to receive medication, 293 had complete information regarding the presence or absence of lifetime ODD. Of those, 115 (39.3%) met DSM-IV criteria for ODD and 178 (60.8%) did not. The high percentage of youths with ODD is consistent with the results of other studies (Biederman et al., 1991, Biederman et al., 2002). The proportions of patients in the ODD and non-ODD groups did not differ significantly with respect to age, sex, ADHD subtype, or

DISCUSSION

ODD is the most common comorbid disorder among youths with ADHD and among the most common conditions in pediatric psychiatry. Yet, there are few reports that specifically address the efficacy of pharmacological interventions in this patient population. Although this study was primarily designed to investigate the treatment of ADHD, it provided a unique opportunity to evaluate moderating effects of ODD symptoms, and the response of ODD symptoms to atomoxetine, as it incorporated measures of ODD

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    This work was sponsored by Eli Lilly and Company. The authors acknowledge Charles Bailey, M.D., Charles Casat, M.D., Joan Busner, M.D., Rakesh Jain, M.D., Anthony Dietrich, M.D., Richard Rubin, M.D., and Lesley Reese, B.A.., for their contributions.

    Correspondence to Dr. Newcorn, Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1230, New York, NY 10029; e-mail: [email protected].

    Disclosure: Dr. Newcorn is an advisor for Celtech Pharmaceuticals, Eli Lilly and Company, Novartis Pharmaceuticals, and Ortho-McNeil Pharmaceuticals; he is a speaker for Eli Lilly and Company, Janssen Pharmaceutical, Novartis Pharmaceuticals, and Ortho-McNeil Pharmaceuticals; he receives grants from Eli Lilly and Company, Ortho Mc-Neil Pharmaceuticals, and Shire Pharmaceuticals; and he is a consultant for Eli Lilly and Company. Dr. Spencer is on the advisory boards of Eli Lilly and Company, GlaxoSmithKline, McNeil Pharmaceutical, Novartis Pharmaceutical, Pfizer Pharmaceutical, and Shire Laboratories, Inc.; he is a speaker for Eli Lilly and Company, GlaxoSmithKline, McNeil Pharmaceutical, Novartis Pharmaceutical, Shire Laboratories, and Wyeth Ayerst; and he receives research support from Eli Lilly and Company, GlaxoSmithKline, McNeil Pharmaceutical, Novartis Pharmaceutical, Pfizer Pharmaceutical, and Shire Laboratories Inc. Dr. Biederman is on the advisory boards of CellTech, Cephalon Pharmaceutical, Eli Lilly and Company, Janssen Pharmaceutical, Johnson & Johnson, McNeil Pharmaceutical, New River Pharmaceuticals, Novartis Pharmaceutical, Noven, Pfizer Pharmaceutical, Sanofi-Synthelabo, and Shire Laboratories Inc.; he is a speaker for Cephalon Pharmaceutical, Eli Lilly and Company, McNeil Pharmaceutical, Novartis Pharmaceutical, Pfizer Pharmaceutical, Shire Laboratories Inc., and Wyeth Ayerst; and he receives research support from Cephalon Pharmaceutical, Eli Lilly and Company, Janssen Pharmaceutical, Neurosearch Pharmaceuticals, Pfizer Pharmaceutical, Shire Laboratories Inc., and the Stanley Medical Institute. Dr. Michelson and Ms. Milton are employees and stakeholders of Eli Lilly and Company.

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