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Treatment of Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and Irritability: Results From the Multimodal Treatment of Children With ADHD (MTA) Study

Doi : 10.1016/j.jaac.2014.10.006 

Lorena Fernández de la Cruz a  , Emily Simonoff a, James J. McGough b, Jeffrey M. Halperin c, L. Eugene Arnold d, Argyris Stringaris a

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Clinically impairing irritability affects 25% to 45% of children with attention-deficit/hyperactivity disorder (ADHD), yet we know little about what interventions are effective in treating children with ADHD and co-occurring irritability. We used data from the Multimodal Treatment of Children with ADHD (MTA) study to address 3 aims: to establish whether irritability in children with ADHD can be distinguished from other symptoms of oppositional defiant disorder (ODD); to examine whether ADHD treatment is effective in treating irritability; and to examine how irritability influences ADHD treatment outcomes.


Secondary analyses of data from the MTA included multivariate analyses, and intent-to-treat random-effects regression models were used.


Irritability was separable from other ODD symptoms. For treating irritability, systematic stimulant treatment was superior to behavioral management but not to routine community care; a combination of stimulants and behavioral treatment was superior to community care and to behavioral treatment alone, but not to medication alone. Irritability did not moderate the impact of treatment on parent- and teacher-reported ADHD symptoms in any of the 4 treatment groups.


Treatments targeting ADHD symptoms are helpful for improving irritability in children with ADHD. Moreover, irritability does not appear to influence the response to treatment of ADHD.

Clinical trial registration information

Multimodal Treatment Study of Children With Attention Deficit and Hyperactivity Disorder (MTA);; NCT00000388.

Le texte complet de cet article est disponible en PDF.

Key Words : irritability, attention-deficit/hyperactivity disorder, oppositional defiant disorder, treatment outcomes


 Clinical guidance is available at the end of this article.
 Supplemental material cited in this article is available online.
 Dr. Fernández de la Cruz was fully supported and Dr. Simonoff was partly supported by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and the Institute of Psychiatry, King’s College London. The Multimodal Treatment Study of Children with ADHD (MTA) has been supported by the following grant numbers: U01MH50440, U01MH50447, U01MH50453, U01MH50454, U01MH50461, U01MH50467, and the following contract numbers: N01MH12004, N01MH12007, N01MH12008, N01MH12009, N01MH12010, N01MH12011, N01MH12012; HHSN271200800003-C, HHSN271200800004-C, HHSN271200800005-C, HHSN271200800006-C, HHSN271200800007-C, HHSN271200800008-C, and HHSN271200800009-C. This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the Department of Health, the MTA Study Investigators, the National Institutes of Health (NIH), the NHS, or the NIHR.
 John Hodsoll, PhD, of King’s College London, served as the statistical expert for this research.
 The authors would like to thank Pablo Vidal-Ribas, MSc, for important insights during analysis of the data. Data used in the preparation of this article (MTA96, version 1) were obtained from the limited access datasets of the MTA, which was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial involving 6 clinical sites. Collaborators from NIMH: Peter S. Jensen, MD (currently at REACH Institute and Mayo Clinic), L. Eugene Arnold, MD, MEd (currently at Ohio State University), Joanne B. Severe, MS (Clinical Trials Operations and Biostatistics Unit, Division of Services and Intervention Research), Benedetto Vitiello, MD (Child and Adolescent Treatment and Preventive Interventions Research Branch), John Richters, PhD (currently at National Institute of Nursing Research), Donald Vereen, MD (currently at National Institute on Drug Abuse). Principal investigators and co-investigators from the 6 sites were: University of California, Berkeley/San Francisco: Stephen P. Hinshaw, PhD (Berkeley), Glen R. Elliott, PhD, MD (San Francisco); Duke University: C. Keith Conners, PhD, Karen C. Wells, PhD, John March, MD, MPH; University of California, Irvine/Los Angeles: James Swanson, PhD (Irvine), Dennis P. Cantwell, MD, (deceased, Los Angeles), Timothy Wigal, PhD (Irvine); Long Island Jewish Medical Center/Montreal Children's Hospital: Howard B. Abikoff, PhD (currently at New York University School of Medicine), Lily Hechtman, MD (McGill University); New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center: Laurence L. Greenhill, MD (Columbia), Jeffrey H. Newcorn, MD (Mount Sinai School of Medicine); University of Pittsburgh: William E. Pelham, PhD (currently at Florida International University), Betsy Hoza, PhD (currently at University of Vermont). Statistical and design consultant: Helena C. Kraemer, PhD (Stanford University). Collaborator from the Office of Special Education Programs/US Department of Education: Ellen Schiller, PhD.
 Disclosure: Dr. McGough has received grant or research support from NIH, NeuroSigma, Inc., Purdue Pharma L.P., and Shire Pharmaceuticals. He has served as a consultant to Akili Interactive Labs, Merck, Neurovance, and Sunovion. He has presented expert testimony for Shire. Dr. Arnold has received research funding from Curemark, Forest, Eli Lilly and Co., Neuropharm, Novartis, Noven, Shire, Young Living, NIH, and Autism Speaks, and has consulted with or been on advisory boards for Gowlings, Neuropharm, Novartis, Noven, Organon, Otsuka, Pfizer, Roche, Seaside Therapeutics, Sigma Tau, Shire, and Tris Pharma, and has received travel support from Noven. Dr. Stringaris has received grant or research support from the Wellcome Trust, the NIHR, and the Department of Health UK. He has received royalties from Cambridge University Press for his book The Maudsley Reader in Phenomenological Psychiatry. Drs. Fernández de la Cruz, Simonoff, and Halperin report no biomedical financial interests or potential conflicts of interest.

© 2014  American Academy of Child and Adolescent Psychiatry. Publié par Elsevier Masson SAS. Tous droits réservés.
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