Treatment of children with attention-deficit/hyperactivity disorder (ADHD) and irritability: results from the multimodal treatment study of children with ADHD (MTA)

Lorena Fernández de la Cruz, Emily Simonoff, James J McGough, Jeffrey M Halperin, L Eugene Arnold, Argyris Stringaris, Lorena Fernández de la Cruz, Emily Simonoff, James J McGough, Jeffrey M Halperin, L Eugene Arnold, Argyris Stringaris

Abstract

Objective: 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 Study of Children With ADHD (MTA) 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.

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

Results: 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.

Conclusion: 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); http://www.clinicaltrials.gov; NCT00000388.

Keywords: attention-deficit/hyperactivity disorder; irritability; oppositional defiant disorder; treatment outcomes.

Copyright © 2015 American Academy of Child & Adolescent Psychaitry. Published by Elsevier Inc. All rights reserved.

Figures

Figure S1
Figure S1
Path analyses of the relation between irritability and headstrong dimensions across time.
Figure 1
Figure 1
Parent-reported irritability response to multimodal treatment in the 4 treatment groups. Note: Beh = Behavioral treatment; CC = Community Comparison; Comb = Combined treatment; MedMgt = Medication management.
Figure 2
Figure 2
Changes in parent-reported attention-deficit/hyperactivity disorder (ADHD) scores in the 4 treatment groups in individuals with high (a) and low (b) irritability. Note: The categorical outcome was generated using a median split into high and low irritability and is used in this figure for purposes of illustration. However, a dimensional irritability variable is used in the statistical models presented in the text. Beh = behavioral treatment; CC = community comparison; Comb = combined treatment; MedMgt = Medication management.

References

    1. Shaw P., Stringaris A., Nigg J., Leibenluft E. Emotion dysregulation in attention deficit hyperactivity disorder. Am J Psychiatry. 2014;171:276–293.
    1. MTA Cooperative Group A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 1999;56:1073–1086.
    1. Polanczyk G., de Lima M.S., Horta B.L., Biederman J., Rohde L.A. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–948.
    1. American Psychiatric Association . 5th edition (DSM-5) American Psychiatric Association; Washington, DC: 2013. Diagnostic and Statistical Manual of Mental Disorders.
    1. Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry. 2011;168:129–142.
    1. Still G.F. Some abnormal psychical conditions in children: excerpts from three lectures. J Atten Disord. 2006;10:126–136.
    1. Barkley R.A. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997;121:65–94.
    1. Stringaris A., Goodman R. Mood lability and psychopathology in youth. Psychol Med. 2009;39:1237–1245.
    1. Greene R.W., Biederman J., Zerwas S., Monuteaux M.C., Goring J.C., Faraone S.V. Psychiatric comorbidity, family dysfunction, and social impairment in referred youth with oppositional defiant disorder. Am J Psychiatry. 2002;159:1214–1224.
    1. Jensen P.S., Hinshaw S.P., Kraemer H.C. ADHD comorbidity findings from the MTA study: comparing comorbid subgroups. J Am Acad Child Adolesc Psychiatry. 2001;40:147–158.
    1. Hechtman L., Abikoff H., Klein R.G. Children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment: impact on parental practices. J Am Acad Child Adolesc Psychiatry. 2004;43:830–838.
    1. Daley D., Van der Oord S., Ferrin M. Behavioral interventions in attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials across multiple outcome domains. J Am Acad Child Adolesc Psychiatry. 2014;53:835–847.
    1. Aebi M., Muller U.C., Asherson P. Predictability of oppositional defiant disorder and symptom dimensions in children and adolescents with ADHD combined type. Psychol Med. 2010;40:2089–2100.
    1. Stringaris A., Goodman R. Longitudinal outcome of youth oppositionality: irritable, headstrong, and hurtful behaviors have distinctive predictions. J Am Acad Child Adolesc Psychiatry. 2009;48:404–412.
    1. Whelan Y.M., Stringaris A., Maughan B., Barker E.D. Developmental continuity of oppositional defiant disorder subdimensions at ages 8, 10, and 13 years and their distinct psychiatric outcomes at age 16 years. J Am Acad Child Adolesc Psychiatry. 2013;52:961–969.
    1. Stringaris A., Goodman R. Three dimensions of oppositionality in youth. J Child Psychol Psychiatry. 2009;50:216–223.
    1. Stringaris A., Zavos H., Leibenluft E., Maughan B., Eley T.C. Adolescent irritability: phenotypic associations and genetic links with depressed mood. Am J Psychiatry. 2012;169:47–54.
    1. Ahmann P.A., Waltonen S.J., Olson K.A., Theye F.W., Van Erem A.J., LaPlant R.J. Placebo-controlled evaluation of Ritalin side effects. Pediatrics. 1993;91:1101–1106.
    1. Childress A.C., Arnold V., Adeyi B. The effects of lisdexamfetamine dimesylate on emotional lability in children 6 to 12 years of age with ADHD in a double-blind placebo-controlled trial. J Atten Disord. 2014;18:123–132.
    1. Coghill D. Adding multimodal behavioural therapy to methylphenidate does not improve ADHD outcomes. Evid Based Ment Health. 2007;10:124.
    1. Manos M.J., Brams M., Childress A.C., Findling R.L., Lopez F.A., Jensen P.S. Changes in emotions related to medication used to treat ADHD. Part I: literature review. J Atten Disord. 2011;15:101–112.
    1. Mongia M., Hechtman L. Cognitive behavior therapy for adults with attention-deficit/hyperactivity disorder: a review of recent randomized controlled trials. Curr Psychiatry Rep. 2012;14:561–567.
    1. Sonuga-Barke E.J., Brandeis D., Cortese S. Nonpharmacological interventions for ADHD: systematic review and meta-analyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry. 2013;170:275–289.
    1. Galanter C.A., Carlson G.A., Jensen P.S. Response to methylphenidate in children with attention deficit hyperactivity disorder and manic symptoms in the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder titration trial. J Child Adolesc Psychopharmacol. 2003;13:123–136.
    1. Galanter C.A., Pagar D.L., Davis M. ADHD and manic symptoms: Diagnostic and treatment implications. Clinical Neuroscience Research. 2005;5:283–294.
    1. Arnold L.E., Abikoff H.B., Cantwell D.P. NIMH collaborative multimodal treatment study of children with ADHD (MTA): design, methodology, and protocol evolution. J Atten Disord. 1997;2:141–158.
    1. Arnold L.E., Abikoff H.B., Cantwell D.P. National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices. Arch Gen Psychiatry. 1997;54:865–870.
    1. Hinshaw S., March J.S., Abikoff H. Comprehensive assessment of childhood attention-deficit hyperactivity disorder in the context of a multisite, multimodal clinical trial. J Atten Disord. 1997;1:217–234.
    1. Swanson J.M. KC Publications; Irvine, CA: 1992. School-Based Assessments and Interventions for ADD Students.
    1. Stringaris A., Goodman R. Mood lability and psychopathology in youth. Psychol Med. 2009;39:1237–1245.
    1. Loeber R., Green S.M., Lahey B.B. Mental-health professionals perception of the utility of children, mothers, and teachers as informants on childhood psychopathology. J Clin Child Psychol. 1990;19:136–143.
    1. Phares V. Accuracy of informants: do parents think that mother knows best? J Abnorm Child Psychol. 1997;25:165–171.
    1. Achenbach T.M. University of Vermont; Burlington, VT: 1991. Manual for the Child Behavior Checklist/4-18 and 1991 Profile. Department of Psychiatry.
    1. Bird H.R., Shaffer D., Fisher P. The Columbia Impairment Scale (CIS)—pilot findings on a measure of global impairment for children and adolescents. Int J Methods Psychiatr Res. 1993;3:167–176.
    1. Stringaris A., Goodman R. The value of measuring impact alongside symptoms in children in adolescents: a longitudinal assessment in a community sample. J Abnorm Child Psychol. 2013;41:1109–1120.
    1. Rowe R., Costello E.J., Angold A., Copeland W.E., Maughan B. Developmental pathways in oppositional defiant disorder and conduct disorder. J Abnorm Psychol. 2010;119:726–738.
    1. Krieger F.V., Polanczyk V.G., Robert G. Dimensions of oppositionality in a Brazilian community sample: testing the DSM-5 proposal and etiological links. J Am Acad Child Adolesc Psychiatry. 2013;52:389–400. e381.
    1. Kolko D.J., Pardini D.A. ODD dimensions, ADHD, and callous-unemotional traits as predictors of treatment response in children with disruptive behavior disorders. J Abnorm Psychol. 2010;119:713–725.
    1. Insel T., Cuthbert B., Garvey M. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010;167:748–751.
    1. Jensen P.S., Hinshaw S.P., Swanson J.M. Findings from the NIMH Multimodal Treatment Study of ADHD (MTA): implications and applications for primary care providers. J Dev Behav Pediatr. 2001;22:60–73.
    1. Blader J.C., Schooler N.R., Jensen P.S. Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. Am J Psychiatry. 2009;166:1392–1401.
    1. The MTA Cooperative Group Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder. Arch Gen Psychiatry. 1999;56:1088–1096.
    1. Landau S., Stahl D. Sample size and power calculations for medical studies by simulation when closed form expressions are not available. Stat Methods Med Res. 2013;22:324–345.
    1. Lenth R.V. Department of Statistics and Actuarial Science, University of Iowa; Iowa City: 2007. Post Hoc Power: Tables and Commentary.
    1. Maughan B., Collishaw S., Stringaris A. Depression in childhood and adolescence. J Can Acad Child Adolesc Psychiatry. 2013;22:35–40.

Source: PubMed

3
Subscribe