Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children With ADHD

OBJECTIVES: The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS: Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol's methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS: Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents.

[1]  T. Wilens,et al.  Characteristics of placebo responders in pediatric clinical trials of attention-deficit/hyperactivity disorder. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[2]  P. Jensen,et al.  Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. , 2009, The American journal of psychiatry.

[3]  Barbara Napolitano,et al.  Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. , 2009, JAMA.

[4]  M. Olfson,et al.  Broadened use of atypical antipsychotics: safety, effectiveness, and policy challenges. , 2009, Health affairs.

[5]  B. Sarvet Improving Mental Health Services in Primary Care: Reducing Administrative and Financial Barriers to Access and Collaboration , 2009, Pediatrics.

[6]  Ann E. Maloney,et al.  Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. , 2008, The American journal of psychiatry.

[7]  E. Coccaro,et al.  Consensus report on impulsive aggression as a symptom across diagnostic categories in child psychiatry: implications for medication studies. , 2007, Journal of the American Academy of Child and Adolescent Psychiatry.

[8]  J. Swanson,et al.  The Texas Children's Medication Algorithm Project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. , 2006, Journal of the American Academy of Child and Adolescent Psychiatry.

[9]  Carmen Moreno,et al.  National trends in the outpatient treatment of children and adolescents with antipsychotic drugs. , 2006, Archives of general psychiatry.

[10]  K. Chang,et al.  Juvenile maladaptive aggression: a review of prevention, treatment, and service configuration and a proposed research agenda. , 2006, The Journal of clinical psychiatry.

[11]  J. Biederman,et al.  Heterogeneity of Irritability in Attention-Deficit/Hyperactivity Disorder Subjects With and Without Mood Disorders , 2005, Biological Psychiatry.

[12]  M. Crismon,et al.  Trends in the use of typical and atypical antipsychotics in children and adolescents. , 2005, Journal of the American Academy of Child and Adolescent Psychiatry.

[13]  H. Feldman,et al.  Treatment of Attention-Deficit/Hyperactivity Disorder: Overview of the Evidence , 2005, Pediatrics.

[14]  J. McGough,et al.  Second-generation antipsychotic medications in children and adolescents. , 2004, Journal of child and adolescent psychopharmacology.

[15]  G. Weiss,et al.  Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment. , 2004, Journal of the American Academy of Child and Adolescent Psychiatry.

[16]  E. Leibenluft,et al.  Defining clinical phenotypes of juvenile mania. , 2003, The American journal of psychiatry.

[17]  S. Glatt,et al.  Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. , 2002, Journal of the American Academy of Child and Adolescent Psychiatry.

[18]  A. Sandler Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings , 2001 .

[19]  Subcommittee on Attention-Deficit,et al.  Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder. , 2001, Pediatrics.

[20]  E. Susser,et al.  Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. , 2000, The American journal of psychiatry.

[21]  Stephen P. Hinshaw,et al.  A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD. , 1999, Archives of general psychiatry.

[22]  H. Abikoff,et al.  Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder. , 1997, Archives of general psychiatry.

[23]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  M. Fava Traditional and alternative research designs and methods in clinical pediatric psychopharmacology. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[25]  J. Swanson,et al.  Medication treatment strategies in the MTA Study: relevance to clinicians and researchers. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[26]  W. Dunlap,et al.  Meta-Analysis of Experiments With Matched Groups or Repeated Measures Designs , 1996 .

[27]  R. Barkley,et al.  Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. , 1990, Pediatrics.

[28]  R. C. Young,et al.  A Rating Scale for Mania: Reliability, Validity and Sensitivity , 1978, British Journal of Psychiatry.

[29]  M. Olfson,et al.  Stimulant dosing for children with ADHD: a medical claims analysis. , 2009, Journal of the American Academy of Child and Adolescent Psychiatry.

[30]  J. Halperin,et al.  Stimulant medications. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  J. Epstein,et al.  Conners Rating Scales-Revised. , 1999 .

[32]  J. Halperin,et al.  Stimulant medications : Current knowledge and unmet needs in pediatrics psychopharmacology , 1999 .

[33]  C. Conners Conners' rating scales-revised : technical manual , 1997 .