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Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data

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Abstract

Rationale

Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40–60% of children with ADHD.

Objectives

This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD.

Methods

Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6–16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6–8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children—Present and Lifetime Versions).

Results

Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response.

Conclusions

Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.

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Acknowledgment

Research funded by Eli Lilly and Company.

Conflict of interest statement

Dr. Joseph Biederman receives/d research support from, is/has been a speaker for, or is/has been on the advisory board for the following Pharmaceutical Companies:

Shire, Eli Lilly, Pfizer, McNeil, Abbott, Bristol-Myers-Squibb, New River Pharmaceuticals, Cephalon, Janssen, Novartis, UCB Pharma, Astra-Zeneca, Forest Laboratories, Glaxo-Smith Kline and Neurosearch

Other Sources of Research Support:

  • Private Foundations

    • Stanley Medical Institute, Inc, Lilly Foundation, Prechter Foundation

  • NIH

    • NIMH, NICHD and NIDA

Dr. Thomas Spencer receives research support from the following sources: Shire Laboratories, Inc and Eli Lilly & Company, Glaxo-Smith Kline, Pfizer Pharmaceutical, McNeil Pharmaceutical, Novartis Pharmaceutical, and NIMH

Dr. Thomas Spencer is a speaker for the following speaker’s bureaus: Glaxo-Smith Kline, Eli Lilly & Company, Novartis Pharmaceutical, Wyeth Ayerst, Shire Laboratories Inc, McNeil Pharmaceutical

Dr. Thomas Spencer is on the advisory board for the following pharmaceutical companies: Shire Laboratories, Inc and Eli Lilly & Company, Glaxo-Smith Kline, Pfizer Pharmaceutical, McNeil Pharmaceutical, and Novartis Pharmaceutical

Dr. Jeffrey Newcorn has not disclosed any conflicts of interest.

Dr. Haitaio Gao is an employee of Eli Lilly & Company.

Dr. Denise Milton is an employee of Eli Lilly & Company.

Dr. Peter D. Feldman is an employee of Eli Lilly & Company.

Dr. Michael M. Witte is an employee of Eli Lilly & Company.

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Authors and Affiliations

  1. Pediatric Psychopharmacology Unit, Massachusetts General Hospital/Harvard Medical School, 55 Fruit St., Yawkey Center for Outpatient Care-6A, Boston, MA, 02114, USA

    Joseph Biederman & Thomas J. Spencer

  2. Department of Psychiatry & Pediatrics, Mt. Sinai School of Medicine, New York, NY, 10029, USA

    Jeffrey H. Newcorn

  3. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Haitao Gao, Denái R. Milton, Peter D. Feldman & Michael M. Witte

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  1. Joseph Biederman
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  2. Thomas J. Spencer
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  3. Jeffrey H. Newcorn
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  4. Haitao Gao
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  5. Denái R. Milton
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Correspondence to Joseph Biederman.

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Biederman, J., Spencer, T.J., Newcorn, J.H. et al. Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data. Psychopharmacology 190, 31–41 (2007). https://doi.org/10.1007/s00213-006-0565-2

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  • DOI: https://doi.org/10.1007/s00213-006-0565-2

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